Affinage

CISD2

CDGSH iron-sulfur domain-containing protein 2 · UniProt Q8N5K1

Length
135 aa
Mass
15.3 kDa
Annotated
2026-06-09
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CISD2 (NAF-1/Miner1) is a redox-active 2Fe-2S iron-sulfur protein that integrates iron handling, ER-mitochondrial calcium transfer, and autophagy/cell-death control at the interface of the ER, outer mitochondrial membrane, and mitochondria-associated membranes (MAMs), with its loss driving mitochondrial degeneration and premature aging (PMID:19451219, PMID:33422617). Structurally it adopts the NEET fold and coordinates two labile 2Fe-2S clusters through a rare Cys3-His motif rather than the originally annotated zinc finger (PMID:19580816); the His114 ligand confers cluster lability, and its mutation abolishes the ability to donate clusters to apo-acceptor proteins and to deliver iron to mitochondria in cells (PMID:23717386, PMID:24914968). Using an inducible dominant-negative H114C system, disruption of CISD2 first perturbs mitochondrial labile iron and then mitochondrial ROS, with calcium changes occurring downstream, establishing iron as the proximal output of cluster transfer (PMID:34547371). CISD2 partners physically with BCL-2 through its BH3/BH4 domains and with the IP3 receptor, SERCA pumps, and Calnexin to govern ER calcium uptake and ER-to-mitochondria calcium transfer: it acts as a BCL-2 co-factor at the ER to suppress Beclin 1-dependent autophagy, yet counteracts BCL-2-mediated inhibition of ER-mitochondrial calcium transfer and contact-site formation (PMID:20010695, PMID:24706857, PMID:39370046, PMID:41299767). Loss of CISD2 produces ER stress, depleted ER calcium, mitochondrial calcium overload, redox imbalance, and sensitization to ferroptosis through dysregulated mitochondrial iron and autophagy-dependent iron accumulation (PMID:23703906, PMID:29928961, PMID:34547371, PMID:36180832). CISD2 stability is set by post-translational control—KAT8-mediated K74 acetylation blocks STUB1-dependent ubiquitination, while PRKN promotes its ubiquitin-dependent degradation (PMID:41687537, PMID:39357167)—and its sustained expression extends mammalian lifespan and protects skeletal muscle, heart, neurons, β-cells, and other tissues from age-associated degeneration (PMID:22661501, PMID:31593566, PMID:40189101).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 2009 High

    Establishing that CISD2 is a mitochondrial protein whose loss causes organelle breakdown defined it as an essential maintainer of mitochondrial integrity and a determinant of aging.

    Evidence Cisd2 knockout mouse with fractionation, histology, and autophagy assays

    PMID:19451219

    Open questions at the time
    • Did not resolve the molecular activity underlying mitochondrial protection
    • ER/MAM localization not yet appreciated
  2. 2009 High

    Solving the crystal structure reclassified CISD2 from a presumed zinc finger to a redox-active 2Fe-2S NEET protein, defining the chemical basis for its function.

    Evidence X-ray crystallography at 2.1 Å with redox potential measurement

    PMID:19580816

    Open questions at the time
    • Structure alone did not establish a cluster acceptor or physiological redox partner
  3. 2009 High

    Identifying CISD2 as an ER-localized BCL-2 partner required for suppressing Beclin 1 autophagy and depressing ER calcium linked its cluster domain to organelle signaling control.

    Evidence Co-IP, knockdown/overexpression, ER Ca2+ and autophagy assays

    PMID:20010695

    Open questions at the time
    • Did not map the BCL-2 binding interface
    • Whether the Fe-S cluster itself participates in calcium control was unresolved
  4. 2012 High

    Tissue phenotyping and a gain-of-function lifespan study showed CISD2 dosage bidirectionally controls aging—loss degenerates muscle, sustained expression extends lifespan.

    Evidence Naf-1 KO and Cisd2 transgenic mice with muscle physiology, lifespan, and mitochondrial readouts

    PMID:22343142 PMID:22661501

    Open questions at the time
    • The molecular event by which CISD2 levels set lifespan was not identified
  5. 2013 High

    Demonstrating in vitro cluster donation to apo-acceptors and cellular iron delivery to mitochondria established CISD2 as a functional iron-sulfur transfer protein, not merely a structural Fe-S holder.

    Evidence In vitro cluster transfer (spectrophotometry, native PAGE) and cellular iron-sensor imaging with small-molecule stabilizers

    PMID:23717386

    Open questions at the time
    • Physiological acceptor protein in cells not defined
    • Link between transfer activity and the calcium/autophagy phenotypes not yet drawn
  6. 2013 High

    Knockout MEF studies tied CISD2 loss to ER calcium depletion, mitochondrial calcium overload, UPR, and redox imbalance reversible by N-acetylcysteine, establishing a coupled calcium/redox dysfunction.

    Evidence Miner1−/− MEFs with Ca2+, redox, UPR, EM, and NAC rescue

    PMID:23703906

    Open questions at the time
    • Causal ordering of iron, ROS, and calcium not established
    • Direct calcium-machinery partners not yet identified
  7. 2013 High

    Showing CISD2 is overexpressed in breast cancer and required for proliferation, mitochondrial performance, and iron/ROS control connected its iron handling to a pro-tumorigenic role.

    Evidence shRNA knockdown in breast cancer cells and xenografts with mitochondrial, iron/ROS, and autophagy readouts

    PMID:23959881

    Open questions at the time
    • Did not distinguish cluster-transfer from protein-interaction contributions to tumor growth
  8. 2014 High

    His114 mutagenesis pinpointed the cluster ligand that confers lability and transfer activity, providing a tool to separate CISD2's enzymatic function from its scaffold role.

    Evidence High-resolution crystallography of native and H114C plus redox and in vitro transfer assays

    PMID:24914968

    Open questions at the time
    • In vivo consequence of stabilized clusters not tested in this study
  9. 2014 High

    Amino-acid-resolution mapping showed CISD2 engages both BH3 and BH4 domains of BCL-2, defining the structural basis of the co-factor interaction.

    Evidence Peptide array, DXMS, and direct coupling analysis

    PMID:24706857

    Open questions at the time
    • Functional consequence of dual-domain binding not resolved here
  10. 2014 Medium

    Adipocyte studies added Gimap5 as a CISD2 membrane partner and linked CISD2 to calcineurin signaling, adipogenesis, and insulin-stimulated glucose uptake.

    Evidence Adipocyte-specific KO mice and Co-IP with metabolic readouts

    PMID:24833725

    Open questions at the time
    • Gimap5 interaction from single lab without reciprocal validation
    • Mechanistic link to cluster chemistry not addressed
  11. 2015 Medium

    Small-molecule destabilization of the CISD2 cluster (MAD-28) phenocopied genetic loss in cancer cells, validating the cluster bond as a druggable functional node.

    Evidence Docking and functional cancer-cell assays compared to shRNA cells

    PMID:25762074

    Open questions at the time
    • Compound selectivity over CISD1 limited
    • In vivo efficacy not established in this study
  12. 2015 Medium

    Further cancer and cardiomyocyte work tied CISD2 loss to iron uptake, metabolic vulnerability, HIF1α stress, and Beclin1–BCL-2-dependent autophagy suppression via AMPK.

    Evidence shRNA/overexpression with iron imaging, metabolic, apoptosis, and Co-IP autophagy assays

    PMID:25689847 PMID:26621032

    Open questions at the time
    • AMPK regulation mechanism not biochemically dissected
    • Single-lab functional readouts
  13. 2016 Medium

    Demonstrating CISD2 silencing accelerates ferroptosis via ferritinophagy and p62/Keap1/NRF2 disruption defined parallel routes by which CISD2 restrains iron-dependent death.

    Evidence shRNA/overexpression with ferritin/p62/Keap1/NRF2 blotting, lysosomal inhibition rescue, and xenograft

    PMID:36180832

    Open questions at the time
    • Direct molecular link between CISD2 and ferritinophagy machinery not shown
    • Single lab
  14. 2017 High

    Identifying CISD2–SERCA2b interaction and regulation of SERCA oxidative state provided a direct mechanism for ER calcium uptake control with disease consequences in liver.

    Evidence Co-IP, SERCA2b activity and oxidation assays in haploinsufficient and overexpressing mice

    PMID:29166610

    Open questions at the time
    • How the Fe-S redox state of CISD2 couples to SERCA oxidation not defined
  15. 2017 Medium

    A patient CISD2 missense mutation linked human disease to enhanced ER-to-mitochondria calcium flux, altered organelle contacts, and a stress-dependent respiratory defect.

    Evidence Patient fibroblasts with Ca2+ imaging, EM, and respirometry

    PMID:28335035

    Open questions at the time
    • Causal mutation effect on cluster chemistry not tested
    • Single patient-derived line
  16. 2017 High

    Showing CISD1 transfers clusters to CISD2 with distinct pH-dependent stabilities revealed a possible NEET cluster relay and divergent cellular roles between the paralogs.

    Evidence Y2H, BiFC, DCA, in vitro transfer, and half-life/pH-stability comparisons

    PMID:28426722 PMID:33916457

    Open questions at the time
    • Physiological significance of CISD1→CISD2 relay in vivo unresolved
  17. 2018 Medium

    CISD2 was placed in ferroptosis and apoptosis regulation in cancer through control of mitochondrial ferrous iron and a mapped iASPP interaction interface targetable by stabilizing peptides.

    Evidence Gain/loss of function ferroptosis assays and peptide-array iASPP interface mapping with apoptosis assays

    PMID:29928961 PMID:30774867

    Open questions at the time
    • iASPP interaction from single lab
    • Therapeutic peptide validated only in vitro/limited models
  18. 2019 High

    Cardiac KO and transgenic mice tied CISD2 to SERCA2a-dependent calcium control, sarcomere/intercalated disc integrity, and cardiac aging delay, generalizing its calcium-homeostasis role across tissues.

    Evidence Cisd2 KO and TG mice with electrophysiology, Ca2+ imaging, SERCA2a activity, and EM

    PMID:31593566

    Open questions at the time
    • Direct CISD2–SERCA2a interaction in heart not biochemically mapped here
  19. 2021 High

    An inducible dominant-negative system established the causal hierarchy—mitochondrial labile iron first, then ROS, then calcium and TXNIP—resolving iron as the proximal output of CISD2 function.

    Evidence Inducible H114C expression with temporal iron, ROS, Ca2+, and TXNIP measurements

    PMID:34547371

    Open questions at the time
    • Identity of the in vivo cluster/iron acceptor downstream of CISD2 still unknown
  20. 2021 Medium

    Defining CISD2's N-terminal ER targeting plus C-terminal KKxx COPI retrieval motif and transmembrane domain explained its ER/MAM residence distinct from mitochondrial CISD1.

    Evidence Domain-swap chimeras with fluorescence localization; review synthesis of three localizations

    PMID:33422617 PMID:34587896

    Open questions at the time
    • Dynamic partitioning between ER, OMM, and MAM under stress not quantified
  21. 2021 Medium

    β-cell and cardiomyocyte studies extended CISD2's iron/ROS-ferroptosis axis to insulin secretion and cardiac iron protection, with chelator/NAC rescue confirming labile iron as the driver.

    Evidence shRNA in INS-1E cells and CISD2-null mouse hearts with iron quantification and pharmacological rescue

    PMID:34439408 PMID:34997963

    Open questions at the time
    • Single-lab studies
    • Mechanism connecting CISD2 loss to ferritin/TfR upregulation not dissected
  22. 2021 Medium

    Epistasis showed CISD2 loss promotes sorafenib-induced ferroptosis in resistant HCC through Beclin1-dependent autophagy, linking its autophagy-suppressor and ferroptosis roles mechanistically.

    Evidence CISD2/Beclin1 double knockdown with ferroptosis and autophagy readouts

    PMID:34485112

    Open questions at the time
    • Single lab
    • Direct CISD2 control point on autophagic iron flux not isolated
  23. 2024 High

    Purified-protein binding showed CISD2 engages BCL-2's BH4 domain with submicromolar affinity and, unexpectedly, counteracts BCL-2's inhibition of ER-mitochondrial calcium transfer while being dispensable for BCL-2 anti-apoptotic and BAX-inhibitory functions.

    Evidence Direct binding assay with purified proteins plus Ca2+ transfer, contact-site, and BAX pore assays

    PMID:39370046

    Open questions at the time
    • Structural basis for CISD2 overriding BCL-2's calcium effect not resolved
  24. 2024 Medium

    Mass spectrometry and KO neutrophil studies added Calnexin as a CISD2 partner regulating calcium homeostasis, broadening its ER calcium-control interactome.

    Evidence MS interaction screen and Cisd2 KO neutrophil functional/Ca2+ assays

    PMID:38627949

    Open questions at the time
    • Calnexin interaction not confirmed by reciprocal Co-IP
    • Single lab
  25. 2024 High

    Identifying KAT8-mediated K74 acetylation that blocks STUB1 ubiquitination, and PRKN-mediated ubiquitin degradation, established post-translational control of CISD2 abundance governing mitochondrial homeostasis and senescence.

    Evidence Acetyl-proteomics, in vitro acetyltransferase assay, mutagenesis, CETSA, Co-IP, and C. elegans validation; Parkin Co-IP/ubiquitination with siRNA rescue

    PMID:39357167 PMID:41687537

    Open questions at the time
    • Upstream signals controlling KAT8 vs STUB1 vs PRKN balance not defined
    • PRKN regulation shown in porcine oocytes only
  26. 2025 High

    β-cell and neuron studies fixed CISD2 as a maintainer of ER-mitochondria contact sites and calcium transfer required for insulin secretion and glutamate-evoked neuronal calcium responses, with transcriptional control by Glis3/Hnf1a and Smad3.

    Evidence Tissue-specific and cell-line KO with Ca2+ imaging, contact-site quantification, respirometry, Co-IP for IP3R, and transcriptomics/ChIP-seq

    PMID:40189101 PMID:41299767 PMID:41413023

    Open questions at the time
    • How CISD2 physically scaffolds ER-mitochondria contacts at IP3R remains unmapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • The unifying question—how CISD2's redox-dependent 2Fe-2S cluster chemistry mechanistically couples to its calcium-transfer scaffold functions and to the identity of its physiological cluster/iron acceptors in vivo—remains open.
  • No in vivo cluster acceptor identified
  • Whether cluster redox state directly gates calcium-partner interactions is untested
  • Structural model of CISD2 at MAM contact sites lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0140104 molecular carrier activity 4 GO:0016209 antioxidant activity 2
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005739 mitochondrion 3
Pathway
R-HSA-5357801 Programmed Cell Death 4 R-HSA-9612973 Autophagy 4 R-HSA-1430728 Metabolism 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
ATP2A2 (SERCA2)BCL-2CANX (CALNEXIN)CISD1 (MITONEET)GIMAP5ITPR (IP3 RECEPTOR)KAT8PRKN
Complex memberships
CISD2 homodimerCISD2–BCL-2 complexmitochondria-associated membrane (MAM) ER-mitochondria contact

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 CISD2 is primarily localized at the mitochondria (outer membrane), and Cisd2 deficiency in mice causes mitochondrial breakdown and dysfunction accompanied by autophagic cell death, leading to a premature aging phenotype. Mitochondrial degeneration is the direct consequence of Cisd2 loss. Cisd2 knockout mouse model with subcellular fractionation/localization, histology, and autophagy assays Genes & development High 19451219
2009 CISD2/Miner1 is a homodimeric protein harboring two redox-active 2Fe-2S clusters bound by a rare Cys3-His motif within the NEET fold. Crystal structure resolved to 2.1 Å confirmed it is not a zinc finger as previously annotated. Redox potentials are proton-coupled (~0 mV at pH 7.5). X-ray crystallography (2.1 Å resolution), biophysical characterization, redox potential measurement Journal of molecular biology High 19580816
2009 NAF-1 (CISD2) is an ER-localized BCL-2-interacting protein; NAF-1 contains a 2Fe-2S coordinating domain necessary (but not sufficient) for BCL-2 interaction. NAF-1 is required for BCL-2 at the ER to antagonize Beclin 1-dependent autophagy during nutrient deprivation. NAF-1 is also required for BCL-2-mediated depression of ER Ca²⁺ stores and associates with the IP3 receptor. Co-immunoprecipitation, knockdown/overexpression functional assays, ER Ca²⁺ measurements, autophagy flux assays The EMBO journal High 20010695
2012 NAF-1 (CISD2) knockout mice display early skeletal muscle degeneration with a shift toward slow-twitch fibers, augmented autophagy, dysregulated calcium homeostasis, and adaptive mitochondrial enlargement. This establishes NAF-1 as required for homeostatic maintenance of skeletal muscle via BCL-2-mediated autophagy regulation and ER Ca²⁺ flux. Naf-1 gene deletion mouse model, muscle physiology, fiber-type analysis, Ca²⁺ measurements, autophagy assays Human molecular genetics High 22343142
2012 Transgenic mice with a persistently high level of Cisd2 show extended median and maximum lifespan without deleterious effects, attenuate age-associated degeneration of skin, skeletal muscle and neurons, and protect mitochondria from age-associated damage. This places Cisd2 as a positive regulator of mammalian lifespan. Cisd2 transgenic (gain-of-function) mice, lifespan analysis, histology, mitochondrial function assays Human molecular genetics High 22661501
2013 NAF-1 (CISD2) can transfer its 2Fe-2S cluster to an apo-acceptor protein in vitro (monitored by spectrophotometry and native PAGE) and transfer iron to intact mitochondria in cell models (monitored by fluorescence imaging with iron sensors). The anti-diabetes drug pioglitazone and resveratrol stabilize NAF-1's labile 2Fe-2S cluster and abrogate its cluster/iron transfer function. In vitro cluster transfer assay (spectrophotometry, native PAGE), cellular iron-transfer assay (fluorescence imaging), small-molecule binding PloS one High 23717386
2013 Loss of Miner1 (CISD2) in mouse embryonic fibroblasts causes ER stress, unfolded protein response, depletion of ER Ca²⁺ stores, increased mitochondrial Ca²⁺ load, increased ROS/RNS, increased GSSG/GSH and NAD⁺/NADH ratios, and altered mitochondrial ultrastructure (increased cristae density, punctate morphology). N-acetylcysteine treatment reversed these abnormalities, implicating sulfhydryl redox status as a key mechanism. Miner1−/− mouse embryonic fibroblasts, ER stress/UPR markers, Ca²⁺ measurements, redox assays, electron microscopy, NAC rescue EMBO molecular medicine High 23703906
2013 NAF-1 (CISD2) and mitoNEET (CISD1) protein levels are elevated in human epithelial breast cancer cells. shRNA suppression of NAF-1 or mitoNEET causes reduced cell proliferation and tumor growth, decreased mitochondrial performance, uncontrolled accumulation of iron and ROS in mitochondria, and activation of autophagy. shRNA knockdown in breast cancer cells and xenograft models, mitochondrial function assays, iron/ROS imaging, autophagy assays Proceedings of the National Academy of Sciences of the United States of America High 23959881
2014 The NAF-1 H114C mutant (His114→Cys in the 2Fe-2S cluster binding site) produces clusters that are 25-fold more stable, have a redox potential 300 mV more negative, and have abolished cluster donation/transfer function, with no global structural differences from wild-type. This identifies His114 as critical for cluster lability and transfer activity. X-ray crystallography (1.65 Å native; 1.58 Å H114C mutant), redox potential measurement, in vitro cluster transfer assay, site-directed mutagenesis Acta crystallographica. Section D, Biological crystallography High 24914968
2014 NAF-1 binds to both the pro- and anti-apoptotic regions (BH3 and BH4 domains) of BCL-2. The interaction interface of the NAF-1–BCL-2 complex was mapped at amino acid resolution using peptide array, deuterium exchange mass spectrometry (DXMS), and direct coupling analysis (DCA). Peptide array screening, deuterium exchange mass spectrometry (DXMS), direct coupling analysis (DCA), functional binding studies Proceedings of the National Academy of Sciences of the United States of America High 24706857
2014 Cisd2 interacts with Gimap5 on mitochondrial and ER membranes and modulates mitochondrial Ca²⁺ uptake, thereby maintaining intracellular Ca²⁺ homeostasis in adipocytes. Loss of Cisd2 increases cytosolic Ca²⁺ and activates Ca²⁺-calcineurin-dependent signaling that inhibits adipogenesis and impairs insulin-stimulated glucose uptake. Adipocyte-specific Cisd2 KO mice, co-immunoprecipitation (interaction with Gimap5), Ca²⁺ measurements, adipogenesis and glucose uptake assays Human molecular genetics Medium 24833725
2015 MAD-28 (a cluvenone derivative) binds to and destabilizes NAF-1 (and mitoNEET) by breaking the coordinative bond between His ligand and the cluster Fe. This causes decreased respiration, decreased mitochondrial membrane potential, and increased mitochondrial iron content in cancer cells, phenocopying NAF-1/mitoNEET shRNA suppression. Molecular docking, functional assays in breast cancer cells (respiration, membrane potential, iron content), shRNA comparison Proceedings of the National Academy of Sciences of the United States of America Medium 25762074
2015 NAF-1 suppression in epithelial breast cancer cells by shRNA activates apoptosis, increases cellular Fe²⁺ uptake, causes a metabolic shift increasing susceptibility to glycolysis inhibition, and activates stress pathways associated with HIF1α. shRNA knockdown in breast cancer cells and xenograft tumors, iron imaging, metabolic assays, apoptosis assays Journal of cell science Medium 26621032
2015 NAF-1 antagonizes starvation-induced autophagy in cardiomyocytes by promoting the Beclin1–BCL-2 interaction (shown by co-immunoprecipitation) and inhibiting AMPK activity. Overexpression of NAF-1 was sufficient to inhibit autophagy and protect cardiomyocytes from nutrient-stress–induced cell death. Co-immunoprecipitation (Beclin1–BCL-2 interaction), NAF-1 overexpression, autophagy assays, AMPK activity assay in neonatal rat cardiomyocytes Cell biology international Medium 25689847
2017 CISD2 interacts with SERCA2b and modulates its Ca²⁺ pump activity via regulation of SERCA2b oxidative modifications, thereby controlling ER Ca²⁺ uptake and maintaining Ca²⁺ homeostasis in hepatocytes. Cisd2 haploinsufficiency disrupts this, causing ER stress and NAFLD/NASH. Co-immunoprecipitation (Cisd2–Serca2b interaction), Serca2b activity assay, oxidative modification analysis, Cisd2 heterozygous and overexpressing mice with liver phenotype readouts Cell reports High 29166610
2017 A novel CISD2 missense mutation (p.Asn72Ser) disturbs cellular Ca²⁺ homeostasis with enhanced Ca²⁺ flux from ER to mitochondria and cytosolic Ca²⁺ abnormalities in patient-derived fibroblasts. This Ca²⁺ dysregulation is associated with increased ER-mitochondria contact, swollen ER lumen, and hyperfused mitochondrial network, and reveals a respiratory chain defect under metabolic stress. Patient-derived fibroblasts, Ca²⁺ imaging, electron microscopy (ER-mitochondria contacts), Seahorse respirometry under galactose medium Human molecular genetics Medium 28335035
2017 mitoNEET (CISD1) and NAF-1 (CISD2) directly interact in mammalian cells (demonstrated by yeast two-hybrid, bimolecular fluorescence complementation, and direct coupling analysis). mitoNEET can transfer its 2Fe-2S clusters to NAF-1 in vitro, consistent with a cluster relay mechanism. Yeast two-hybrid, in vivo BiFC, DCA, in vitro cluster transfer assay, shRNA double-knockdown lines with ROS/iron imaging PloS one High 28426722
2018 CISD2 overexpression confers resistance to sulfasalazine-induced ferroptosis in head and neck cancer cells, while CISD2 silencing increases sensitivity via increased mitochondrial ferrous iron and lipid ROS accumulation, identifying CISD2 as a regulator of mitochondrial iron and ferroptosis susceptibility. CISD2 overexpression and siRNA knockdown, ferroptosis assays (lipid ROS, mitochondrial iron), mouse xenograft models Cancer letters Medium 29928961
2018 iASPP and NAF-1 (CISD2) interact in cancer cells during apoptosis. The interaction interface maps to residues 764–778 of iASPP binding to a surface groove of NAF-1, identified by peptide array screening and computational methods. A peptide corresponding to iASPP 764–780 stabilizes the NAF-1 cluster, inhibits NAF-1–iASPP interaction, and inhibits staurosporine-induced apoptosis in breast and prostate cancer cells. Peptide array screening, computational docking, Co-IP in cells, peptide functional assay (apoptosis inhibition, IC50 determination) Chemical science Medium 30774867
2019 Cisd2 deficiency in the heart causes intercalated disc defects, mitochondrial and sarcomere degeneration, and disrupts Ca²⁺ homeostasis via dysregulation of Serca2a activity, resulting in increased basal cytosolic Ca²⁺ and mitochondrial Ca²⁺ overload in cardiomyocytes. Persistent high Cisd2 expression delays cardiac aging. Cisd2 KO and transgenic mice, cardiac electrophysiology, Ca²⁺ imaging, Serca2a activity assay, electron microscopy PLoS biology High 31593566
2021 Inducible disruption of CISD2 function (using dominant-negative H114C) causes an immediate disruption in mitochondrial labile iron (mLI), followed by enhanced mitochondrial ROS. Alterations in cytosolic and ER Ca²⁺ levels occur only after the changes in mLI and mROS, indicating iron is upstream of Ca²⁺ signaling. CISD2 disruption also triggers TXNIP expression in a mLI-dependent manner. Inducible expression system for dominant-negative CISD2 H114C, mitochondrial labile iron imaging, mROS assays, Ca²⁺ measurements, TXNIP expression analysis; temporal hierarchy established Free radical biology & medicine High 34547371
2021 CISD2 is targeted to the ER by its N-terminal sequence and is retained there by the combined action of a C-terminal COPI-binding KKxx ER retrieval motif and an ER-targeting transmembrane domain, distinguishing it from CISD1 (mitoNEET) which uses different targeting motifs to reach mitochondria. Recombinant antibodies, localization of protein chimeras (domain swaps), fluorescence microscopy BMC molecular and cell biology Medium 34587896
2021 CISD2 protein can be localized on the ER, outer mitochondrial membrane (OMM), and mitochondria-associated membrane (MAM), and plays a crucial role in regulating cytosolic Ca²⁺ homeostasis, ER integrity, and mitochondrial function. These three localizations underlie its roles in lifespan, cell death, and disease. Subcellular fractionation, multiple mouse models (reviewed), functional assays for Ca²⁺, ER stress, mitochondria Biochimica et biophysica acta. Molecular cell research Medium 33422617
2021 NAF-1 repression in INS-1E pancreatic β-cells inhibits insulin secretion, impairs mitochondrial and ER structure/function, and induces ferroptosis-like features. Combined treatment with deferiprone (iron chelator) and N-acetylcysteine (glutathione precursor) restores insulin secretion and repairs mitochondrial and ER structure by reducing mitochondrial labile iron and ROS. shRNA repression in INS-1E cells, insulin secretion assay, iron chelation/NAC rescue, ferroptosis inhibitor (ferrostatin-1), mitochondrial/ER ultrastructure Antioxidants (Basel, Switzerland) Medium 34439408
2021 CISD2 knockdown promotes ferroptosis through two parallel mechanisms: (1) ferritinophagy-dependent ferritin degradation causing free iron accumulation; (2) degradation of p62 that increases Keap1-NRF2 binding leading to NRF2 ubiquitination/degradation, reducing FTH and HO-1 expression and increasing oxidative stress. shRNA and overexpression in cancer cells, confocal microscopy, western blot for ferritin/p62/Keap1/NRF2, lysosomal inhibition rescue, in vivo xenograft Cellular & molecular biology letters Medium 36180832
2021 CISD2 knockdown promotes sorafenib-induced ferroptosis in resistant HCC cells via uncontrolled autophagy (autophagy-mediated iron accumulation), in a Beclin1-dependent manner. Beclin1 co-knockdown attenuates the ferroptotic effect of CISD2 knockdown. shRNA knockdown of CISD2 and Beclin1, ferroptosis assays (ROS, MDA, GSH, iron), western blot for autophagy markers Frontiers in oncology Medium 34485112
2021 CISD2 deficiency in cardiomyocytes (CISD2-null mice) causes accumulation of high levels of iron, increased transferrin receptor and ferritin, and features of cardiomyocyte aging, demonstrating that CISD2 protects cardiomyocytes from iron overaccumulation. CISD2-null mice, proteomics, transmission electron microscopy, iron and transferrin receptor/ferritin measurement FEBS letters Medium 34997963
2021 CISD2 and mitoNEET exhibit distinct intracellular half-lives and differ in the pH sensitivity of their Fe-S cluster stability and ability to transfer clusters in vitro, despite close structural homology, suggesting distinct cellular roles. Cellular half-life measurement, in vitro cluster stability and transfer assays at varying pH, expression profiling across tissues Biomedicines Medium 33916457
2024 CISD2 directly interacts with BCL-2's BH4 domain with submicromolar affinity (using purified proteins). CISD2 overexpression enhanced BCL-2-mediated suppression of cytosolic IP3R-mediated Ca²⁺ release. Most strikingly, CISD2 counteracts BCL-2-mediated inhibition of ER-mitochondrial Ca²⁺ transfer: BCL-2 overexpression reduced ER-mitochondrial Ca²⁺ transfer and contact sites, but co-expression of CISD2 abolished these BCL-2 effects. CISD2 was not essential for BCL-2's anti-apoptotic function or BAX pore formation inhibition. Purified protein direct binding assay (submicromolar affinity), Ca²⁺ signaling assays (cytosolic and mitochondrial), ER-mitochondria contact site quantification, BAX pore formation assay, loss-of-function in cells Biochimica et biophysica acta. Molecular cell research High 39370046
2024 Cisd2 interacts with Calnexin (identified by mass spectrometry), and this interaction along with Calnexin–SERCA modulates Ca²⁺ homeostasis in neutrophils. Cisd2 KO mice neutrophils display Ca²⁺ dysregulation and functional defects despite elevated numbers. Mass spectrometry (Cisd2–Calnexin interaction), Cisd2 KO mouse neutrophil functional assays, Ca²⁺ measurements BMB reports Medium 38627949
2024 KAT8/MSL acetyltransferase complex acetylates CISD2 at K74, preventing STUB1-mediated ubiquitination and degradation at K105. Acetylation at K74 preserves mitochondrial homeostasis. Ginsenoside Rg5 binds KAT8 and promotes CISD2 acetylation, maintaining mitochondrial function and alleviating senescence. SILAC-based acetyl-proteomics, Co-IP, GST pull-down, in vitro lysine acetyltransferase assay, site-directed mutagenesis (K74, K105), cycloheximide chase, CETSA, mitochondrial function assays, C. elegans genetic validation Phytomedicine : international journal of phytotherapy and phytopharmacology High 41687537
2024 PRKN (Parkin) E3 ubiquitin ligase mediates ubiquitination and proteasomal degradation of CISD2 in porcine oocytes. ETA treatment decreases PRKN expression, reducing CISD2 ubiquitination and increasing CISD2 levels. CISD2 inhibits IP3R-mediated Ca²⁺ release (in a BCL-2-dependent manner) at MAMs, and its knockdown blocks ETA's ability to inhibit IP3R. Immunoprecipitation (CISD2–PRKN interaction, ubiquitination), siRNA knockdown of CISD2, transcriptomic sequencing, IP3R functional assays, MAM imaging Theriogenology Medium 39357167
2025 Beta-cell–specific Cisd2 KO in mice disrupts glucose-induced extracellular Ca²⁺ influx, impairing Ca²⁺-mediated insulin secretory signaling, causing mitochondrial dysfunction and reduced insulin secretion. Cisd2 deficiency also suppresses Glis3 and Hnf1a transcription regulators critical for β-cell function. β-cell–specific Cisd2 KO mice, CRISPR-mediated Cisd2KO MIN6 β-cell line, Ca²⁺ imaging, insulin secretion assays, transcriptomic analysis Molecular metabolism High 40189101
2025 CISD2 loss in HeLa cells reduces ER-mitochondrial Ca²⁺ transfer. In human iPSC-derived cortical neurons, Cisd2 deficiency severely reduces glutamate-evoked cytosolic and mitochondrial Ca²⁺ responses due to loss of ER-mitochondria contact sites, causing mitochondrial dysfunction (reduced OCR, ATP, membrane potential) and increased apoptotic sensitivity. CISD2 interacts with IP3 receptors. Cisd2 KO HeLa cells and human iPSC-derived cortical neurons, Ca²⁺ imaging (cytosolic and mitochondrial), ER-mitochondria contact site quantification, Seahorse respirometry, Co-IP (Cisd2–IP3R interaction), apoptosis assays Acta neuropathologica communications High 41299767
2025 Smad3 regulates CISD2 expression by directly binding its promoter region (ChIP-seq validated). CISD2 overexpression in Smad3-knockdown mesenchymal bladder cancer cells rescues ferroptosis markers (Fe²⁺, ROS, lipid peroxides, MDA and GSH levels), placing CISD2 downstream of Smad3 in a ferroptosis-regulatory pathway. ChIP-seq, RNA-seq, Smad3 knockdown, CISD2 overexpression rescue, ferroptosis assays, clinical specimen correlation, xenograft Cell death & disease Medium 41413023
2025 The NAF-1 44-67 cancer-targeting peptide (derived from CISD2 residues 44–67) targets the CISD2/NAF-1 protein inside cancer cells and disrupts its homodimeric structure. Dimers of the peptide have higher anticancer activity than monomers. A homologous peptide from CISD1 (mitoNEET) has no cancer-killing activity, indicating specificity for NAF-1 structure. Peptide treatment of cancer cells, structural disruption assays of CISD2 dimer, comparison with CISD1 peptide, dimer vs. monomer activity assays Cancer letters Medium 40118242
2014 Genetic epistasis in Drosophila shows that altered function of the CISD2 orthologue (cisd2) modifies the phenotypic effects of overexpressing PPT1 and CLN3 orthologues on eye morphology, and overexpression of CLN3 combined with cisd2 loss-of-function disrupts locomotor ability, placing cisd2 in a functional network with lysosomal storage disease genes. Drosophila genetics (RNAi knockdown, overexpression, epistasis/modifier screen), eye morphology assay, locomotor assay Biology open Low 24705017
2015 CISD2 knockdown in neural cells by siRNA causes increased iNOS expression and decreased BCL-2 expression in an LPS-challenged model, suggesting CISD2 functions as a suppressor of nitric oxide/inflammatory signaling upstream of BCL-2. CISD2 knockdown reduces the anti-inflammatory and anti-apoptotic effects of curcumin. siRNA knockdown in neural cells, LPS challenge, iNOS and BCL-2 western blot, SCI rat model Injury Low 26387034
2020 CISD2 knockdown in EOC microglial cells causes augmented proinflammatory signaling, decreased M2 phenotype markers (Arg-1, Ym1, IL-10, BCL2) and increased NF-κB p65 DNA-binding activity, placing CISD2 as an upstream anti-inflammatory modulator of the NF-κB pathway in microglia. siRNA knockdown in EOC microglial cells, cytokine/marker western blot and RT-PCR, NF-κB ELISA DNA-binding assay Frontiers in aging neuroscience Low 33005144

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes & development 231 19451219
2009 Antagonism of Beclin 1-dependent autophagy by BCL-2 at the endoplasmic reticulum requires NAF-1. The EMBO journal 225 20010695
2018 CISD2 inhibition overcomes resistance to sulfasalazine-induced ferroptotic cell death in head and neck cancer. Cancer letters 223 29928961
2013 NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth. Proceedings of the National Academy of Sciences of the United States of America 172 23959881
2009 Crystal structure of Miner1: The redox-active 2Fe-2S protein causative in Wolfram Syndrome 2. Journal of molecular biology 103 19580816
2013 Wolfram Syndrome protein, Miner1, regulates sulphydryl redox status, the unfolded protein response, and Ca2+ homeostasis. EMBO molecular medicine 98 23703906
2022 Inhibition of CISD2 promotes ferroptosis through ferritinophagy-mediated ferritin turnover and regulation of p62-Keap1-NRF2 pathway. Cellular & molecular biology letters 96 36180832
2012 Bcl-2-associated autophagy regulator Naf-1 required for maintenance of skeletal muscle. Human molecular genetics 91 22343142
2014 Cisd2 modulates the differentiation and functioning of adipocytes by regulating intracellular Ca2+ homeostasis. Human molecular genetics 85 24833725
2012 A persistent level of Cisd2 extends healthy lifespan and delays aging in mice. Human molecular genetics 85 22661501
2017 CISD2 Haploinsufficiency Disrupts Calcium Homeostasis, Causes Nonalcoholic Fatty Liver Disease, and Promotes Hepatocellular Carcinoma. Cell reports 67 29166610
2018 Resveratrol-Induced Downregulation of NAF-1 Enhances the Sensitivity of Pancreatic Cancer Cells to Gemcitabine via the ROS/Nrf2 Signaling Pathways. Oxidative medicine and cellular longevity 66 29765509
2010 A role for the CISD2 gene in lifespan control and human disease. Annals of the New York Academy of Sciences 66 20649540
2021 CISD2 maintains cellular homeostasis. Biochimica et biophysica acta. Molecular cell research 65 33422617
2015 The Fe-S cluster-containing NEET proteins mitoNEET and NAF-1 as chemotherapeutic targets in breast cancer. Proceedings of the National Academy of Sciences of the United States of America 65 25762074
2009 Cisd2 mediates mitochondrial integrity and life span in mammals. Autophagy 61 19717971
2014 A novel CISD2 intragenic deletion, optic neuropathy and platelet aggregation defect in Wolfram syndrome type 2. BMC medical genetics 58 25056293
2017 A novel CISD2 mutation associated with a classical Wolfram syndrome phenotype alters Ca2+ homeostasis and ER-mitochondria interactions. Human molecular genetics 57 28335035
2021 CISD2 Promotes Resistance to Sorafenib-Induced Ferroptosis by Regulating Autophagy in Hepatocellular Carcinoma. Frontiers in oncology 56 34485112
2014 Integrated strategy reveals the protein interface between cancer targets Bcl-2 and NAF-1. Proceedings of the National Academy of Sciences of the United States of America 52 24706857
2012 BCL2-CISD2: An ER complex at the nexus of autophagy and calcium homeostasis? Autophagy 49 22617439
2015 Activation of apoptosis in NAF-1-deficient human epithelial breast cancer cells. Journal of cell science 45 26621032
2019 Cisd2 is essential to delaying cardiac aging and to maintaining heart functions. PLoS biology 43 31593566
2013 Nutrient-deprivation autophagy factor-1 (NAF-1): biochemical properties of a novel cellular target for anti-diabetic drugs. PloS one 41 23717386
2017 Interactions between mitoNEET and NAF-1 in cells. PloS one 40 28426722
2022 Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science 38 35871686
2020 NAF-1 Inhibition by Resveratrol Suppresses Cancer Stem Cell-Like Properties and the Invasion of Pancreatic Cancer. Frontiers in oncology 38 32766132
2014 Cisd2 mediates lifespan: is there an interconnection among Ca²⁺ homeostasis, autophagy, and lifespan? Free radical research 38 24974737
2021 Cisd2 slows down liver aging and attenuates age-related metabolic dysfunction in male mice. Aging cell 37 34811857
2021 Disrupting CISD2 function in cancer cells primarily impacts mitochondrial labile iron levels and triggers TXNIP expression. Free radical biology & medicine 35 34547371
2016 Recovery of oxidative stress-induced damage in Cisd2-deficient cardiomyocytes by sustained release of ferulic acid from injectable hydrogel. Biomaterials 35 27392289
2015 CISD2 serves a novel role as a suppressor of nitric oxide signalling and curcumin increases CISD2 expression in spinal cord injuries. Injury 35 26387034
2017 CISD2 promotes the proliferation of glioma cells via suppressing beclin‑1‑mediated autophagy and is targeted by microRNA‑449a. Molecular medicine reports 34 28983596
2020 Mitochondria and Calcium Homeostasis: Cisd2 as a Big Player in Cardiac Ageing. International journal of molecular sciences 33 33287440
2019 Protective Effects of CISD2 and Influence of Curcumin on CISD2 Expression in Aged Animals and Inflammatory Cell Model. Nutrients 31 30934593
2020 Function of WFS1 and WFS2 in the Central Nervous System: Implications for Wolfram Syndrome and Alzheimer's disease. Neuroscience and biobehavioral reviews 30 32949681
2020 Upregulation of Cisd2 attenuates Alzheimer's-related neuronal loss in mice. The Journal of pathology 29 31837018
2017 CISD2 enhances the chemosensitivity of gastric cancer through the enhancement of 5-FU-induced apoptosis and the inhibition of autophagy by AKT/mTOR pathway. Cancer medicine 29 28857517
2017 Comparative proteomic profiling reveals a role for Cisd2 in skeletal muscle aging. Aging cell 28 29168286
2014 A point mutation in the [2Fe-2S] cluster binding region of the NAF-1 protein (H114C) dramatically hinders the cluster donor properties. Acta crystallographica. Section D, Biological crystallography 28 24914968
2021 Uniting the divergent Wolfram syndrome-linked proteins WFS1 and CISD2 as modulators of Ca2+ signaling. Science signaling 27 34582248
2024 Hesperetin activates CISD2 to attenuate senescence in human keratinocytes from an older person and rejuvenates naturally aged skin in mice. Journal of biomedical science 23 38263133
2021 CISD2 plays a role in age-related diseases and cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 23 33752060
2021 Cisd2 plays an essential role in corneal epithelial regeneration. EBioMedicine 23 34740104
2015 Dysregulation of Mitochondrial Functions and Osteogenic Differentiation in Cisd2-Deficient Murine Induced Pluripotent Stem Cells. Stem cells and development 22 26230298
2021 Cisd2 Protects the Liver from Oxidative Stress and Ameliorates Western Diet-Induced Nonalcoholic Fatty Liver Disease. Antioxidants (Basel, Switzerland) 21 33916843
2022 Rejuvenation: Turning Back Time by Enhancing CISD2. International journal of molecular sciences 20 36430496
2020 Cisd2: a promising new target in Alzheimer's disease†. The Journal of pathology 19 32207855
2020 Wild Bitter Melon Exerts Anti-Inflammatory Effects by Upregulating Injury-Attenuated CISD2 Expression following Spinal Cord Injury. Behavioural neurology 18 33062068
2024 CISD2 regulates oxidative stress and mitophagy to maintain the balance of the follicular microenvironment in PCOS. Redox report : communications in free radical research 14 39010730
2021 A Combined Drug Treatment That Reduces Mitochondrial Iron and Reactive Oxygen Levels Recovers Insulin Secretion in NAF-1-Deficient Pancreatic Cells. Antioxidants (Basel, Switzerland) 14 34439408
2020 Exercise and the Cisd2 Prolongevity Gene: Two Promising Strategies to Delay the Aging of Skeletal Muscle. International journal of molecular sciences 14 33260577
2015 NAF-1 antagonizes starvation-induced autophagy through AMPK signaling pathway in cardiomyocytes. Cell biology international 13 25689847
2023 Targeting Ca2+-dependent pathways to promote corneal epithelial wound healing induced by CISD2 deficiency. Cellular signalling 12 37315750
2018 Cisd2 haploinsufficiency: A driving force for hepatocellular carcinoma. Molecular & cellular oncology 12 30250893
2018 The anti-apoptotic proteins NAF-1 and iASPP interact to drive apoptosis in cancer cells. Chemical science 12 30774867
2022 High Expression of CISD2 in Relation to Adverse Outcome and Abnormal Immune Cell Infiltration in Glioma. Disease markers 10 35493303
2022 CISD2 Promotes Proliferation of Colorectal Cancer Cells by Inhibiting Autophagy in a Wnt/β-Catenin-Signaling-Dependent Pathway. Biochemical genetics 10 36008699
2021 New Insights of the NEET Protein CISD2 Reveals Distinct Features Compared to Its Close Mitochondrial Homolog mitoNEET. Biomedicines 10 33916457
2020 CISD2 Attenuates Inflammation and Regulates Microglia Polarization in EOC Microglial Cells-As a Potential Therapeutic Target for Neurodegenerative Dementia. Frontiers in aging neuroscience 10 33005144
2017 A donor splice site mutation in CISD2 generates multiple truncated, non-functional isoforms in Wolfram syndrome type 2 patients. BMC medical genetics 10 29237418
2023 Ferroptosis-associated gene CISD2 suppresses colon cancer development by regulating tumor immune microenvironment. PeerJ 9 37304867
2019 Homozygosity mapping and direct sequencing identify a novel pathogenic variant in the CISD2 gene in an Iranian Wolfram syndrome family. Acta diabetologica 9 31309279
2014 Genetic studies in Drosophila and humans support a model for the concerted function of CISD2, PPT1 and CLN3 in disease. Biology open 9 24705017
2021 Intracellular targeting of Cisd2/Miner1 to the endoplasmic reticulum. BMC molecular and cell biology 8 34587896
2021 Rejuvenating the Aging Heart by Enhancing the Expression of the Cisd2 Prolongevity Gene. International journal of molecular sciences 8 34768917
2024 CISD2 counteracts the inhibition of ER-mitochondrial calcium transfer by anti-apoptotic BCL-2. Biochimica et biophysica acta. Molecular cell research 7 39370046
2021 Cisd2 Preserves the Youthful Pattern of the Liver Proteome during Natural Aging of Mice. Biomedicines 7 34572415
2024 Bulk RNA-sequencing, single-cell RNA-sequencing analysis, and experimental validation reveal iron metabolism-related genes CISD2 and CYP17A1 are potential diagnostic markers for recurrent pregnancy loss. Gene 6 38244949
2024 Inhibition of CISD2 enhances sensitivity to doxorubicin in diffuse large B-cell lymphoma by regulating ferroptosis and ferritinophagy. Frontiers in pharmacology 6 39605902
2022 The [2Fe-2S] protein CISD2 plays a key role in preventing iron accumulation in cardiomyocytes. FEBS letters 6 34997963
2020 Cryogen spray cooling mitigates inflammation and injury-induced CISD2 decline in rat spinal cord hemisection model. Journal of integrative neuroscience 6 33378836
2024 Cisd2 deficiency impairs neutrophil function by regulating calcium homeostasis via Calnexin and SERCA. BMB reports 5 38627949
2024 CISD2 downregulation participates in the ferroptosis process of human ovarian SKOV-3 cells through modulating the wild type p53-mediated GLS2/SAT1/SLC7A11 and Gpx4/TRF signaling pathway. Tissue & cell 5 38991271
2024 Dexmedetomidine mitigates lidocaine-induced spinal cord injury by repressing ferritinophagy-mediated ferroptosis by increasing CISD2 expression in rat models. Journal of bioenergetics and biomembranes 5 39168950
2024 Eicosatrienoic acid enhances the quality of in vitro matured porcine oocytes by reducing PRKN-mediated ubiquitination of CISD2. Theriogenology 5 39357167
2024 A preliminary study unveils CISD2 as a ferroptosis-related therapeutic target for recurrent spontaneous abortion through immunological analysis and two-sample mendelian randomization. Journal of reproductive immunology 4 38678819
2023 Lipid-Specific Direct Translocation of the Cell-Penetrating Peptide NAF-144-67 across Bilayer Membranes. The journal of physical chemistry. B 4 36827970
2023 CISD2 promotes lung squamous carcinoma cell migration and invasion via the TGF-β1-induced Smad2/3 signaling pathway. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 4 37249759
2023 CISD2 transcriptional activated by transcription factor E2F7 promotes the malignant progression of cervical cancer. Journal of molecular histology 4 37615745
2021 Behavioral characterization of a novel Cisd2 mutant mouse. Behavioural brain research 4 33610659
2018 Generation of Human-Induced Pluripotent Stem Cells from Wolfram Syndrome Type 2 Patients Bearing the c.103 + 1G>A CISD2 Mutation for Disease Modeling. Stem cells and development 4 29239282
2025 CISD2-mediated mitochondrial dysfunction and iron redistribution contributes to ferroptosis in arsenic-induced nonalcoholic steatohepatitis. Ecotoxicology and environmental safety 3 39808878
2025 Targeting the SMAD3/CISD2 axis suppresses bladder cancer progression by promoting ferroptosis in mesenchymal-like bladder cancer cells. Cell death & disease 3 41413023
2024 CircSLC25A16 facilitates the development of non-small-cell lung cancer through the miR-335-5p/CISD2 axis. Thoracic cancer 3 38803052
2024 Loss of Cisd2 Exacerbates the Progression of Age-Related Hearing Loss. Aging and disease 3 39226169
2025 Wolfram syndrome 2 gene (CISD2) deficiency disrupts Ca2+-mediated insulin secretion in β-cells. Molecular metabolism 2 40189101
2025 Hesperetin Alleviates Bleomycin-Induced Pulmonary Fibrosis by Modulating Cellular Senescence and Promoting Impaired Autophagy in a CISD2-Dependent Manner. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 41001804
2024 Overexpression of CISD2 alleviates septic acute kidney injury via activating Sonic Hedgehog signaling pathway. Cellular and molecular biology (Noisy-le-Grand, France) 2 38814213
2024 Proteome-wide association studies have predicted that the protein abundance of LSM6, GMPPB, ICA1L, and CISD2 is associated with attention-deficit/hyperactivity disorder. European child & adolescent psychiatry 2 38954053
2024 Immunoinformatic-based drug design utilizing hesperetin to target CISD2 activation for liver aging in humans. Biogerontology 2 39196437
2013 Sequence variants of the aging gene CISD2 and the risk for Alzheimer's disease. Journal of the Formosan Medical Association = Taiwan yi zhi 2 26154755
2026 Ginsenoside Rg5 targets the KAT8-CISD2 axis to maintain mitochondrial homeostasis and antagonize senescence. Phytomedicine : international journal of phytotherapy and phytopharmacology 1 41687537
2025 Unraveling the molecular mechanism underlying the anticancer activity of CISD2/NAF-144-67. Cancer letters 1 40118242
2025 Cisd1 synergizes with Cisd2 to modulate protein processing by maintaining mitochondrial and ER homeostasis. Aging 1 40349253
2025 Activation of CISD2 as a protective strategy against doxorubicin-induced cardiotoxicity. Redox biology 1 40876442
2025 CISD2 ensures adequate ER-mitochondrial coupling, critically supporting mitochondrial function in neurons. Acta neuropathologica communications 1 41299767
2025 Immunoinformatics-guided approach to target CISD2 upregulation using (2R)-2-[3,4-bis(oxidanyl)phenyl]-6-oxidanyl-2,3-dihydrochromen-4-one(6J6) for treating chronic kidney disease: enhancing CISD2 upregulation to combat CKD through 6J6. In silico pharmacology 1 41393792
2025 Unraveling the molecular mechanism underlying the anticancer activity of CISD2/NAF-1 44-67. bioRxiv : the preprint server for biology 0 39829923
2025 Cisd2 delays atrial aging via a modulation of calcium homeostasis that mitigates atrial myopathy. Cell communication and signaling : CCS 0 40841648

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