Affinage

Showing BLOC1S1 — GCN5L1 is a alias.

BLOC1S1

Biogenesis of lysosome-related organelles complex 1 subunit 1 · UniProt P78537

Length
153 aa
Mass
17.3 kDa
Annotated
2026-06-09
61 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BLOC1S1 (BLOS1/GCN5L1) is a small multifunctional scaffold that operates in two distinct cellular arenas: as a shared subunit of the BLOC-1 and BORC complexes governing endolysosomal organelle biogenesis and transport, and as a mitochondrial regulator of protein acetylation and metabolism (PMID:15102850, PMID:22309213, PMID:41887224). It was first defined as a BLOC-1 subunit whose stability is interdependent with the other subunits (Pallidin, Muted, Cappuccino, Dysbindin) and the accessory partner KXD1, with loss producing lysosome-related organelle defects reminiscent of Hermansky-Pudlak syndrome (PMID:15102850, PMID:22554196). In the endolysosomal system it drives BORC-dependent anterograde lysosome positioning and autophagy, with most pathogenic BLOC1S1 variants showing reduced complex assembly and impaired rescue of lysosome transport, a phenotype more severe for BORC than for BLOC-1 function (PMID:41887224). It coordinates microtubule motors for organelle movement, acting as an adaptor linking kinesin-3 (KIF13A) and kinesin-2 (KIF3) for recycling-endosome transport that delivers LDLR to the plasma membrane, and recruiting the ARL8B-KIF5B machinery together with the actin nucleator WHAMM to enable mTORC1-dependent autophagic lysosome reformation (PMID:33179593, PMID:33629936). It also supports lysosomal degradative trafficking of EGFR via SNX2 and TSG101 (PMID:25183008). Although it lacks intrinsic enzymatic activity, mitochondrial BLOC1S1/GCN5L1 promotes acetylation of numerous targets — respiratory chain proteins counteracting SIRT3, fatty-acid-oxidation enzymes (HADHA, LCAD, SCAD) and PDH, the fission factor Drp1, TFAM, Rictor, and glutaminase — thereby tuning oxidative metabolism, mitochondrial biogenesis and turnover, cristae remodeling, and retrograde ROS-ERK-FoxO1 signaling (PMID:22309213, PMID:28526709, PMID:30323061, PMID:31138772, PMID:36474281, PMID:39390372, PMID:40338741). Its mRNA is a specific RIDD substrate of IRE1, and IRE1-driven Blos1 degradation repositions lysosomes to the MTOC to promote ESCRT-dependent microautophagy of protein aggregates and to control intracellular pathogen trafficking (PMID:25870107, PMID:30787040, PMID:35587649, PMID:36044348). Loss-of-function or dysregulation links BLOC1S1 to disease: pathogenic variants cause a lysosome-transport disorder, and its upregulation contributes to mitochondrial deficits in ALS (PMID:41383013, PMID:41887224).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 2004 High

    Established BLOC1S1 as a bona fide structural subunit of the BLOC-1 complex, defining its founding role in lysosome-related organelle biogenesis.

    Evidence Co-IP, size exclusion chromatography, yeast two-hybrid, and pallid mouse genetics

    PMID:15102850

    Open questions at the time
    • Did not resolve BLOC-1 architecture at residue level
    • Did not address non-BLOC-1 functions
  2. 2012 High

    Identified BLOC1S1/GCN5L1 as a mitochondrial-enriched regulator that supports protein acetylation antagonizing SIRT3, opening an entirely separate functional axis from BLOC-1.

    Evidence Knockdown, mitochondrial reconstitution, in vitro acetylation and respiration assays

    PMID:22309213

    Open questions at the time
    • Whether GCN5L1 itself catalyzes acetylation or scaffolds an acetyltransferase was unresolved
    • Specific substrate residues not mapped
  3. 2012 Medium

    Connected BLOC1S1 to the accessory factor KXD1 and to lysosome-related organelle integrity, reinforcing subunit-interdependent stability.

    Evidence In vitro binding assay and Kxd1 KO mice with LRO ultrastructural defects

    PMID:22554196

    Open questions at the time
    • Mechanism by which KXD1 stabilizes BLOS1 unclear
    • Mild phenotype leaves redundancy unaddressed
  4. 2013 Medium

    Showed GCN5L1 negatively regulates mitochondrial turnover by restraining a coordinated TFEB/PGC-1α program, linking it to autophagy and biogenesis balance.

    Evidence KO/knockdown with gene expression and mitochondrial content assays, dual-knockdown epistasis

    PMID:24356961

    Open questions at the time
    • Direct molecular target connecting GCN5L1 to TFEB not identified
    • Single lab
  5. 2014 Medium

    Demonstrated a BLOC1S1 role in endosomal sorting by linking it to SNX2 and TSG101 to drive lysosomal degradation of EGFR.

    Evidence Reciprocal Co-IP, KD/KO MEFs and rescue, EGFR trafficking assay

    PMID:25183008

    Open questions at the time
    • Whether this reflects BLOC-1, BORC, or retromer-specific activity unclear
    • Single lab
  6. 2015 Medium

    Defined BLOC1S1 mRNA as a specific, conserved RIDD target cleaved by IRE1 at a mapped site, establishing post-transcriptional control under ER stress.

    Evidence qPCR, bioinformatics, cleavage-site mutagenesis, IRE1 RNase inhibitor in cancer cells

    PMID:25870107

    Open questions at the time
    • Functional consequence for acute ER-stress recovery was negative
    • Downstream effect of Blos1 loss not yet defined here
  7. 2017 High

    Extended GCN5L1's metabolic reach by showing it promotes acetylation of FAO enzymes and PDH and a TDH-coupled acetylation of KBP, regulating cardiac fatty acid oxidation and stem-cell mitochondrial biogenesis.

    Evidence Knockdown with acetylation/activity assays, HFD mice; acetylation-site mapping and Fbxo15/Kif1B genetic epistasis in mESCs

    PMID:28319092 PMID:28526709

    Open questions at the time
    • Mechanism of substrate selection by GCN5L1 unresolved
    • Tissue-specificity of acetylation targets unclear
  8. 2017 High

    Established GCN5L1 as a node in mitochondrial retrograde signaling controlling hepatic gluconeogenesis via ROS-ERK-FoxO1.

    Evidence Liver-specific KO, ERK inhibition, mitochondrial-targeted reconstitution, ROS and proteasome assays

    PMID:28900165

    Open questions at the time
    • Direct mitochondrial acetylation substrate triggering ROS not pinpointed
    • Single study
  9. 2018 Medium

    Linked GCN5L1 to cytoskeletal acetylation and lysosome positioning through αTAT1 and RanBP2, bridging its mitochondrial and trafficking roles.

    Evidence Co-IP, knockdown phenocopy, α-tubulin acetylation and lysosome positioning assays, HDAC inhibitor

    PMID:30333138

    Open questions at the time
    • Whether GCN5L1 directly acetylates tubulin vs. recruits αTAT1 unclear
    • Single lab
  10. 2018 High

    Mapped specific HADHA acetylation sites regulated by GCN5L1/SIRT3, tying GCN5L1 to hepatic lipid handling and protection from diet-induced steatosis.

    Evidence Transgenic OE, proteomic site mapping, stable KD, liver-specific KO, enzymatic assays

    PMID:30323061

    Open questions at the time
    • In vivo stoichiometry of site occupancy unclear
    • Single lab
  11. 2019 High

    Resolved the functional purpose of IRE1-mediated Blos1 decay: lysosome repositioning to the MTOC enables ESCRT-dependent microautophagy of ubiquitinated aggregates under ER stress.

    Evidence Uncleavable Blos1 mutant rescue, live imaging, ESCRT loss-of-function, aggregate detection

    PMID:30787040

    Open questions at the time
    • How reduced BLOS1 mechanistically shifts lysosome polarity not fully defined
    • Link to BORC disassembly not yet shown here
  12. 2019 Medium

    Showed GCN5L1 binds and acetylates Rictor to sustain mTORC2/Akt signaling and limit mitochondrial ROS in cardiomyocyte stress.

    Evidence Co-IP, knockdown, Rictor acetylation rescue, hypoxia-reoxygenation survival assay

    PMID:31138772

    Open questions at the time
    • Acetylation site on Rictor not mapped in this study
    • Single lab
  13. 2020 High

    Defined BLOS1 as a dual kinesin adaptor (KIF13A and KIF3) coordinating long-range anterograde recycling-endosome transport that controls LDLR surface delivery and plasma LDL clearance.

    Evidence Co-IP, hepatocyte-specific KO mice, LDLR trafficking and LDL measurement, live imaging

    PMID:33179593

    Open questions at the time
    • How BLOS1 switches between motor types unclear
    • Relationship to BORC complex in this role not defined
  14. 2021 High

    Established BLOC1S1 as required for autophagic lysosome reformation by recruiting ARL8B-KIF5B and WHAMM to drive mTORC1-dependent lysosomal tubulation.

    Evidence Liver-specific KO, reconstitution rescue, Co-IP, concurrent KIF5B depletion epistasis, MTORC1 inhibition, live imaging

    PMID:33629936

    Open questions at the time
    • Order of WHAMM actin nucleation vs. KIF5B recruitment unclear
    • Single lab
  15. 2021 Low

    Clarified that GCN5L1 lacks intrinsic acetyltransferase activity and instead functions as a multi-complex scaffold supporting acetylation.

    Evidence Functional-domain alignment and review of prior experimental data

    PMID:32599084

    Open questions at the time
    • Review without new primary experiments
    • Identity of the catalytic enzyme(s) it scaffolds not established
  16. 2022 Medium

    Expanded the metabolic substrate repertoire (glutaminase, TFAM, GPD2) and connected GCN5L1 to mTORC1 activity, mitochondrial biogenesis, and redox-coupled gluconeogenesis.

    Evidence Hepatocyte-specific KO, acetylation/activity assays, PLA and Co-IP, glucose production and redox assays, HCC tumor models

    PMID:35538890 PMID:35802941 PMID:36474281

    Open questions at the time
    • Whether TFAM/glutaminase acetylation is direct or scaffold-mediated unresolved
    • Single labs per substrate
  17. 2022 High

    Generalized the RIDD-BLOS1 axis to host-pathogen conflict, showing IRE1-driven Blos1 decay disrupts BORC assembly and lysosome positioning to either restrict or be exploited by intracellular pathogens.

    Evidence RIDD-deficient cells and IRE1α knock-in mice, Bloc1s1 KO, BORC assembly and lysosome imaging, Brucella and coronavirus infection assays

    PMID:35587649

    Open questions at the time
    • How BLOS1 loss biochemically destabilizes BORC not detailed
    • Generalizability beyond tested pathogens unclear
  18. 2022 Medium

    Reinforced the aggregate-clearance role by showing Blos1 decay enhances ESCRT-dependent microautophagy of mutant Huntingtin in neurons.

    Evidence Uncleavable Blos1 mutant, ESCRT loss-of-function, primary neuron mHTT quantification

    PMID:36044348

    Open questions at the time
    • Whether basal BLOS1 levels limit clearance in disease unclear
    • Single lab replicating prior work
  19. 2022 Medium

    Linked BLOC1S1 lysosomal control to hepatic lipid storage, with depletion raising lysosomal content and lipolysis independent of canonical lipophagy.

    Evidence Liver-specific KO mice and iPSC-derived hepatocytes with lysosomal and lipid readouts

    PMID:36535215

    Open questions at the time
    • Mechanism coupling BLOC1S1 loss to lysosome biogenesis unclear
    • Single lab
  20. 2023 Medium

    Demonstrated functionally separable mitochondrial vs. non-mitochondrial GCN5L1 pools in alveolar cells, where mitochondrial reconstitution rescues organelle morphology but not trafficking.

    Evidence CRISPR KO, mitochondrial-targeted reconstitution, TEM, RNA-seq, lipid measurement

    PMID:37936104

    Open questions at the time
    • Molecular basis of pool partitioning not defined
    • Single lab
  21. 2024 Medium

    Added Drp1 acetylation as a GCN5L1 output controlling mitochondrial fission and neuronal apoptosis downstream of CDK5-AMPK in ischemia.

    Evidence Co-IP, KD/OE, AMPK inhibition, mitochondrial morphology, dMCAO mouse model

    PMID:39390372

    Open questions at the time
    • Drp1 acetylation site not mapped
    • Single lab
  22. 2024 Medium

    Showed GCN5L1 stabilizes Rictor via acetylation against proteasomal degradation under hypoxia and modulates ferroptosis sensitivity via CISD1-dependent mitochondrial iron homeostasis in HCC.

    Evidence Co-IP, KD/OE with proteasome inhibition; CRISPR KO with sorafenib sensitivity, ROS, lipid peroxidation, tumor models

    PMID:38281616 PMID:38918793

    Open questions at the time
    • Whether CISD1 regulation is acetylation-dependent unclear
    • Single labs
  23. 2025 Medium

    Defined a cristae-remodeling role via GCN5L1 interaction with YME1L and MIC13/MICOS that degrades cristae junctions and promotes adipocyte expansion in obesity.

    Evidence Interactome Co-IP, adipose-specific KO, EM cristae analysis, OXPHOS activity assays

    PMID:40338741

    Open questions at the time
    • Whether MIC13 degradation requires acetylation unclear
    • Single lab
  24. 2025 Medium

    Implicated GCN5L1 in stimulus-dependent mitochondria-to-cytoplasm translocation that stabilizes PPARγ by K289 acetylation, and in ALS pathology where its upregulation impairs motor-neuron mitochondria.

    Evidence Subcellular fractionation, Co-IP, K289 site mapping, PPARγ-KI mice; iPSC motor neurons, splice-switching ASO, ALS mouse survival, postmortem tissue

    PMID:41383013 PMID:41574605

    Open questions at the time
    • Trigger and machinery for translocation not defined
    • Causality of GCN5L1 upregulation in human ALS unproven
  25. 2026 High

    Connected BLOC1S1 to human Mendelian disease, showing pathogenic variants impair BORC/BLOC-1 assembly and lysosome transport with BORC function more affected than BLOC-1.

    Evidence BLOC1S1-KO cells and iPSC neurons, variant rescue, lysosome transport, autophagy, pigmentation, complex-assembly assays

    PMID:41887224

    Open questions at the time
    • Genotype-phenotype correlation across variants incomplete
    • Mechanism of differential BORC vs BLOC-1 sensitivity unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single non-catalytic scaffold partitions between mitochondrial acetylation and endolysosomal trafficking roles, and which acetyltransferase(s) GCN5L1 actually scaffolds.
  • Identity of the catalytic enzyme supported by GCN5L1 unknown
  • Regulation of subcellular pool partitioning undefined
  • Structural basis for shared BORC/BLOC-1 subunit usage not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005739 mitochondrion 3 GO:0005764 lysosome 3 GO:0005768 endosome 2 GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-9609507 Protein localization 3 R-HSA-9612973 Autophagy 3
Partners
ARL8BKIF13AKIF3KIF5BKXD1RICTORSNX2WHAMM
Complex memberships
BLOC-1BORC

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 BLOS1 (BLOC1S1) was identified as a novel subunit of the BLOC-1 complex. Using co-immunoprecipitation and size exclusion chromatography, BLOS1 co-fractionates and co-immunoprecipitates with previously known BLOC-1 subunits (Pallidin, Muted, Cappuccino, Dysbindin). Yeast two-hybrid analyses revealed a network of binary interactions involving BLOS1 and other BLOC-1 subunits. Steady-state levels of BLOS1 are reduced in pallid mouse cells, indicating interdependence of complex subunit stability. Co-immunoprecipitation, size exclusion chromatography, yeast two-hybrid, genetic mouse model (pallid) The Journal of biological chemistry High 15102850
2012 GCN5L1/BLOC1S1 functions as a component of the mitochondrial acetyltransferase program. It is mitochondrial-enriched, displays homology to a prokaryotic acetyltransferase, and counters the deacetylation activity of SIRT3. Genetic knockdown of GCN5L1 blunts global mitochondrial protein acetylation; reconstitution in intact mitochondria restores it. GCN5L1 interacts with and promotes acetylation of SIRT3 respiratory chain targets and reverses SIRT3 effects on mitochondrial protein acetylation, respiration, and bioenergetics. Genetic knockdown, mitochondrial reconstitution, in vitro acetylation assay, respiratory measurement, interaction studies The Biochemical journal High 22309213
2013 Genetic deletion of GCN5L1 directly increases expression and activity of TFEB (master regulator of autophagy) and concurrently induces PGC-1α (mitochondrial biogenesis co-activator), resulting in increased mitochondrial turnover. Knockdown of either TFEB or PGC-1α leads to decreased expression of the other, showing they act coordinately to maintain mitochondrial content in response to GCN5L1 modulation. Genetic knockout/knockdown, gene expression analysis, mitochondrial content assay, epistasis via dual knockdown The Journal of biological chemistry Medium 24356961
2014 BLOS1 interacts with SNX2 (retromer subunit) and TSG101 (ESCRT-I component) to mediate lysosomal trafficking of EGFR. BLOS1 knockdown delays EGFR degradation and causes accumulation of endolysosomes; this is rescued by BLOS1 overexpression. BLOS1 KO mouse embryonic fibroblasts phenocopy the knockdown. Co-immunoprecipitation, knockdown and rescue experiments, KO MEFs, EGFR trafficking assay The Journal of biological chemistry Medium 25183008
2015 BLOC1S1 mRNA is a specific, conserved RIDD (regulated IRE1-dependent mRNA decay) target. Under conditions of IRE1 hyperactivation, BLOC1S1 mRNA is specifically cleaved by IRE1 at guanine 444. This cleavage is temporally separate from XBP1 splicing and occurs after depletion of unspliced XBP1. However, expression of an uncleavable BLOC1S1 mutant or inhibition of RIDD did not affect cellular recovery from acute ER stress. qPCR, bioinformatics, cleavage-site mutagenesis, IRE1 RNase inhibitor, cancer cell lines Molecular and cellular biology Medium 25870107
2017 GCN5L1 promotes acetylation of mitochondrial fatty acid oxidation enzymes (LCAD, SCAD, HADHA) and pyruvate dehydrogenase in cardiac tissue in response to high-fat diet. GCN5L1 knockdown decreases acetylation of these enzymes and reduces fatty acid oxidation in H9C2 cardiac cells, indicating GCN5L1-mediated acetylation promotes FAO enzyme activity in the heart. Genetic knockdown, immunoprecipitation-based acetylation assay, enzymatic activity measurement, fatty acid oxidation assay, mouse HFD model American journal of physiology. Heart and circulatory physiology Medium 28526709
2017 TDH (responsible for mitochondrial acetyl-CoA production in mESCs) and GCN5L1 cooperate to acetylate Lys501 of KBP, enabling its recognition and degradation by the E3 ligase Fbxo15. This pathway limits mitochondrial biogenesis in mouse embryonic stem cells; defects in KBP degradation cause unscheduled increase in mitochondrial biogenesis and enhanced respiration. Co-IP, acetylation mapping, genetic epistasis (Fbxo15 KO, Kif1Bα silencing), mESC differentiation assays Nature cell biology High 28319092
2017 Hepatic GCN5L1 ablation reduces fasting glucose and blunts gluconeogenesis. Mechanistically, GCN5L1 loss reduces FoxO1 protein levels via proteasome-dependent degradation and via ROS-mediated ERK1/2 phosphorylation. ERK inhibition restores FoxO1, gluconeogenic enzyme expression, and glucose production. Reconstitution of mitochondrial-targeted GCN5L1 blunts mitochondrial ROS and ERK activation, and restores FoxO1 and gluconeogenesis, establishing GCN5L1 as a regulator of mitochondrial ROS–ERK–FoxO1 retrograde signaling. Liver-specific knockout, pharmacological ERK inhibition, mitochondrial-targeted GCN5L1 reconstitution, ROS measurement, proteasome inhibition Nature communications High 28900165
2018 GCN5L1 interacts with the α-tubulin acetyltransferase αTAT1 and with RanBP2. GCN5L1-mediated α-tubulin acetylation in hepatocytes is αTAT1-dependent. RanBP2 possesses a tubulin-binding domain that recruits GCN5L1 to α-tubulin. Genetic silencing of RanBP2 phenocopies GCN5L1 depletion by reducing α-tubulin acetylation. GCN5L1 depletion promotes perinuclear lysosome accumulation, and HDAC inhibition partially restores lysosomal positioning. Co-immunoprecipitation, genetic knockdown, α-tubulin acetylation assay, lysosome positioning assay, HDAC inhibitor Journal of cell science Medium 30333138
2018 GCN5L1 promotes acetylation of HADHA (mitochondrial trifunctional protein subunit α) in the liver, specifically at K350, K383, and K406. Transgenic GCN5L1 overexpression in mouse liver increases HADHA acetylation and GCN5L1/SIRT3 co-regulated sites were mapped by proteomics. Stable GCN5L1 knockdown in HepG2 cells reduced HADHA acetylation and increased FAO enzyme activities. Liver-specific GCN5L1 KO mice were protected from HFD-induced hepatic lipid accumulation. Transgenic overexpression, proteomic acetylation mapping, stable KD, liver-specific KO mice, enzymatic activity assay The Journal of biological chemistry High 30323061
2019 Degradation of Blos1 mRNA by IRE1 leads to repositioning of late endosomes/lysosomes to the microtubule-organizing center (MTOC) in response to ER stress in mouse cells. Overriding Blos1 degradation (expressing uncleavable Blos1) leads to ER stress sensitivity and accumulation of ubiquitinated protein aggregates; efficient degradation of these aggregates requires independent trafficking to the cell center and ESCRT-mediated microautophagy. Thus Blos1 downregulation by IRE1 promotes LE-mediated microautophagy and protects cells from aggregate toxicity. IRE1-mediated mRNA degradation, overexpression of uncleavable mutant, live imaging of lysosome positioning, ubiquitinated aggregate detection, ESCRT loss-of-function The Journal of cell biology High 30787040
2019 GCN5L1 directly binds the mTORC2 component Rictor. Loss of GCN5L1 in cardiomyocytes reduces Rictor acetylation, impairs Akt phosphorylation, elevates mitochondrial ROS, and reduces cell viability in response to hypoxia-reoxygenation. Restoring Rictor acetylation in GCN5L1-depleted cells reduces mitochondrial ROS and increases cell survival. Co-immunoprecipitation, genetic knockdown, Rictor acetylation assay, Akt signaling assay, hypoxia-reoxygenation cell survival assay The Biochemical journal Medium 31138772
2020 BLOS1 interacts with kinesin-3 motor KIF13A and acts as a new adaptor for kinesin-2 motor KIF3 to coordinate kinesin-3 and kinesin-2 during long-range anterograde transport of recycling endosomes (REs) to the plasma membrane along microtubules. Loss of BLOS1 in hepatocyte-specific KO mice reduces membrane LDLR and impairs LDL clearance from plasma. Co-immunoprecipitation, hepatocyte-specific KO mice, LDLR trafficking assay, plasma LDL measurement, live imaging eLife High 33179593
2021 BLOC1S1/GCN5L1 is required for autophagic lysosome reformation (ALR). In liver-specific bloc1s1 KO hepatocytes, nutrient deprivation fails to initiate ALR due to blunted lysosomal tubulation. BLOC1S1 interacts with the ARL8B–KIF5B complex to recruit KIF5B to autolysosomes and interacts with the actin nucleation-promoting factor WHAMM. Genetic reintroduction of BLOC1S1 rescues lysosomal tubulation, but not when KIF5B is concurrently depleted, establishing epistasis. MTORC1 inhibition also abolishes BLOC1S1 reconstitution-mediated rescue of tubulation. Liver-specific KO, genetic reconstitution, Co-immunoprecipitation (ARL8B, KIF5B, WHAMM), concurrent KIF5B depletion (epistasis), MTORC1 inhibition, live imaging of lysosomal tubulation Autophagy High 33629936
2012 BLOS1 interacts with KXD1, a novel 20 kDa coiled-coil protein, as confirmed by in vitro binding assays. In Kxd1 knockout mice, BLOS1 protein levels are significantly reduced, and mild defects in melanosomes and platelet dense granules (lysosome-related organelles) are observed, mimicking a mild form of Hermansky-Pudlak syndrome. Naïve Bayesian analysis, in vitro binding assay, Kxd1 KO mice, ultrastructural analysis of LROs Traffic (Copenhagen, Denmark) Medium 22554196
2022 GCN5L1 promotes acetylation and inactivation of glutaminase isoforms GLS1 and GLS2 in the liver and increases enzyme oligomerization. GCN5L1 depletion in HCC cells promotes mTORC1 activation and cell proliferation; GCN5L1 levels inversely correlate with mTORC1 activity and glutaminase activity in human HCC tumors. Genetic KO, hepatocyte-specific KO mice, GLS1/2 acetylation and activity assay, orthotopic tumor assay, mTORC1 signaling analysis Clinical and translational medicine Medium 35538890
2022 GCN5L1 (BLOC1S1) acetylates TFAM at K76. This acetylation inhibits TFAM binding to TOM70, thereby reducing TFAM import into mitochondria and impairing mitochondrial biogenesis. In AKI, GCN5L1 is upregulated, leading to hyperacetylation of TFAM at K76. Renal tubule-specific GCN5L1 knockdown attenuates AKI-induced mitochondrial impairment. Acetylated proteomics, Duolink proximity ligation assay, Co-immunoprecipitation, site-specific acetylation mapping, genetic KD in vivo Journal of translational medicine Medium 36474281
2022 Brucella activates RIDD (regulated IRE1-dependent decay) of Bloc1s1 mRNA to subvert innate immune defense. Inactivation of Bloc1s1 impairs BORC assembly, causing perinuclear trafficking of Brucella-containing vacuoles and enhanced susceptibility. The RIDD-resistant Bloc1s1 variant maintains BORC integrity and promotes centrifugal lysosome trafficking, resulting in lysosomal destruction of Brucella. Coronavirus MHV also exploits the RIDD–BLOS1 axis to promote replication. RIDD-deficient cell lines, RIDD-incompetent IRE1α knock-in mice, Bloc1s1 KO, BORC assembly assay, lysosome trafficking imaging, infection susceptibility assay eLife High 35587649
2022 BLOC1S1 depletion in hepatocytes increases lysosomal content, lysosomal lipid uptake, and lipolysis independently of macro- and chaperone-mediated lipophagy but dependent on total lysosome content. Genetic induction of lysosomal biogenesis in transformed hepatocytes replicates depletion of intracellular lipid stores. Liver-specific KO mice, iPSC-derived hepatocyte-like cells (HLCs), lysosomal enzyme activity assay, lipid staining, lysosomal content measurement Biochemical and biophysical research communications Medium 36535215
2022 IRE1-mediated degradation of Blos1 mRNA enhances ESCRT-dependent endosomal microautophagy of mutant Huntingtin (mHTT), reducing accumulation of mHTT aggregates. Overriding Blos1 degradation causes excessive mHTT aggregate accumulation in cultured cells and primary neurons. Before large aggregates form, mHTT is degraded via ESCRT-dependent, macroautophagy-independent microautophagy, and this pathway is enhanced by Blos1 degradation. Uncleavable Blos1 mutant overexpression, ESCRT loss-of-function, primary neuron culture, mHTT aggregate quantification Molecular biology of the cell Medium 36044348
2022 GCN5L1 directly binds GPD2 (glycerol phosphate dehydrogenase 2, a key component of the mitochondrial glycerol phosphate shuttle) and modulates its activity. GCN5L1 deletion dramatically inhibits glucose production from glycerol and lactate due to increased cytosolic redox state, linked to altered GPD2 activity. Co-immunoprecipitation, genetic deletion, glucose production assay, cytosolic redox measurement, GPD2 activity assay Biochemical and biophysical research communications Medium 35802941
2024 GCN5L1 promotes Drp1 acetylation to enhance mitochondrial fission in ischemic neuronal cells. Ischemia/hypoxia induces CDK5 upregulation which activates AMPK, facilitating GCN5L1–Drp1 interaction and subsequent Drp1 acetylation; this promotes mitochondrial fission and neuronal apoptosis. GCN5L1 knockdown reduces Drp1 acetylation and mitochondrial fission; AMPK inhibition also blocks Drp1 acetylation. GCN5L1 overexpression enhances Drp1 acetylation and fission. Co-immunoprecipitation, genetic KD/OE, AMPK inhibition, CDK5 pathway analysis, mitochondrial morphology assay, dMCAO mouse model Molecular medicine (Cambridge, Mass.) Medium 39390372
2023 GCN5L1 is present in both mitochondria and lamellar bodies (LBs) in alveolar epithelial cells. Knockout of GCN5L1 results in smaller, accumulated LB-like organelles indicating both biogenesis and trafficking defects. Reconstruction of mitochondrial GCN5L1 rescues organelle morphology but not the trafficking defect, indicating distinct roles for mitochondrial vs. non-mitochondrial GCN5L1. Loss of GCN5L1 also activates the ROS-Erk-Foxo1-Cebpα axis to downregulate surfactant-related genes. CRISPR KO, lentiviral reconstitution (mitochondrial-targeted), TEM, immunofluorescence, RNA-seq, ELISA, lipid measurement Cellular & molecular biology letters Medium 37936104
2024 GCN5L1 mediates acetylation of Rictor in cardiomyocytes, preventing its proteasomal degradation under hypoxic stress. GCN5L1 knockdown reduces Rictor acetylation and protein levels after hypoxia; GCN5L1 overexpression blocks hypoxia-induced Rictor loss. This protects cytoprotective Akt/mTORC2 signaling. Rictor degradation under hypoxia is proteasome-mediated and antagonized by increased acetylation. Co-immunoprecipitation, knockdown/overexpression, Rictor acetylation assay, proteasome inhibition, Akt/mTORC2 signaling measurement Cellular signalling Medium 38281616
2025 GCN5L1 coordinates with YME1L protease and the MICOS component MIC13 to remodel mitochondrial cristae in white adipocytes. GCN5L1 protein interacts with MIC13 and YME1L in the mitochondrial intermembrane space; its accumulation during high-fat diet feeding facilitates MIC13/MICOS degradation and cristae disassembly, reducing OXPHOS complex stability and enhancing adipocyte expansion. White adipose-specific GCN5L1 KO increases cristae content, stabilizes OXPHOS complexes, and resists obesity. Protein interactome analysis, Co-IP, adipose-specific KO mice, electron microscopy for cristae analysis, OXPHOS complex activity assay Cell reports Medium 40338741
2025 BLOC1S1/GCN5L1 is significantly upregulated in ALS patient-derived motor neurons, postmortem motor cortices, and spinal cords of ALS mouse models. BLOC1S1 depletion (via splice-switching antisense oligonucleotides inducing NMD) rescues mitochondrial respiration and ALS-relevant cellular deficits in iPSC-derived motor neurons from diverse genetic backgrounds, and extends survival in an ALS mouse model. iPSC-derived motor neurons, splice-switching ASO, mitochondrial respiration assay, ALS mouse model survival, postmortem patient tissue Molecular therapy Medium 41383013
2026 BLOC1S1 KO impairs anterograde transport of lysosomes and autophagy in both non-neuronal cells and iPSC-derived neurons. Most pathogenic BLOC1S1 variants exhibit reduced expression, decreased assembly with BORC/BLOC-1 subunits, and/or impaired rescue of lysosome transport and autophagy in BLOC1S1-KO cells. Evidence indicates loss of BLOC1S1 leads to more pronounced deficits in BORC function than in BLOC-1 function. BLOC1S1 KO cell lines, iPSC-derived neurons, transfection rescue experiments, lysosome transport assay, autophagy assay, BORC/BLOC-1 assembly assay, melanocytic pigmentation assay American journal of human genetics High 41887224
2026 GCN5L1 undergoes stimulus-dependent translocation from mitochondria to the cytoplasm during lipid overload and high-fat diet feeding. Cytoplasmic GCN5L1 binds PPARγ and promotes its acetylation at K289, protecting PPARγ from ubiquitination-mediated proteasomal degradation. PPARγ-K289 mutation reduces ubiquitination of PPARγ and exacerbates liver steatosis in mice, establishing GCN5L1 as a mitochondrial retrograde signal controlling hepatic lipid synthesis via PPARγ stabilization. Subcellular fractionation, Co-immunoprecipitation, acetylation site mapping (K289), PPARγ-K289 mutant mice, transcriptome and proteome analysis, ubiquitination assay JCI insight Medium 41574605
2021 GCN5L1 does not possess intrinsic acetyltransferase activity (as shown by functional-domain sequence alignment and experimental studies), yet supports protein acetylation in mitochondria and cytosol by acting as a subunit of numerous multiprotein complexes. Functional domain analysis, experimental studies (cited in review) Biochimica et biophysica acta. Gene regulatory mechanisms Low 32599084
2024 GCN5L1 deficiency in HCC cells increases sorafenib sensitivity by downregulating the mitochondrial iron transporter CISD1, leading to mitochondrial iron accumulation, increased cellular and lipid ROS, and ferroptosis. GCN5L1 modulates mitochondrial iron homeostasis via regulation of CISD1 expression. CRISPR KO, sorafenib sensitivity assay, CISD1 expression analysis, ROS measurement, lipid peroxidation assay, in vivo orthotopic tumor model Journal of translational medicine Medium 38918793
2025 BLOC1S1 sequesters TDP-43 in the cytoplasm, inhibiting its nuclear translocation-dependent ATG7 mRNA stabilization and autophagy induction. Co-immunoprecipitation confirmed direct interaction between BLOC1S1 and TDP-43. BLOC1S1 overexpression attenuates autophagy and reduces autolysosome formation in goat spermatogonial stem cells challenged with Brucella LPS. Co-immunoprecipitation, subcellular localization (immunofluorescence), BLOC1S1 overexpression, TEM, LC3B-II/I ratio, RNA-seq and proteomics Advanced science Low 40936170

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Identification of snapin and three novel proteins (BLOS1, BLOS2, and BLOS3/reduced pigmentation) as subunits of biogenesis of lysosome-related organelles complex-1 (BLOC-1). The Journal of biological chemistry 221 15102850
2012 Identification of a molecular component of the mitochondrial acetyltransferase programme: a novel role for GCN5L1. The Biochemical journal 187 22309213
2013 GCN5-like protein 1 (GCN5L1) controls mitochondrial content through coordinated regulation of mitochondrial biogenesis and mitophagy. The Journal of biological chemistry 111 24356961
2017 Acetylation of mitochondrial proteins by GCN5L1 promotes enhanced fatty acid oxidation in the heart. American journal of physiology. Heart and circulatory physiology 77 28526709
2018 The protein acetylase GCN5L1 modulates hepatic fatty acid oxidation activity via acetylation of the mitochondrial β-oxidation enzyme HADHA. The Journal of biological chemistry 76 30323061
2017 GCN5L1 modulates cross-talk between mitochondria and cell signaling to regulate FoxO1 stability and gluconeogenesis. Nature communications 59 28900165
2019 Degradation of Blos1 mRNA by IRE1 repositions lysosomes and protects cells from stress. The Journal of cell biology 58 30787040
2014 Biogenesis of lysosome-related organelles complex-1 subunit 1 (BLOS1) interacts with sorting nexin 2 and the endosomal sorting complex required for transport-I (ESCRT-I) component TSG101 to mediate the sorting of epidermal growth factor receptor into endosomal compartments. The Journal of biological chemistry 54 25183008
2018 GCN5L1/BLOS1 Links Acetylation, Organelle Remodeling, and Metabolism. Trends in cell biology 53 29477615
2015 Cleavage of BLOC1S1 mRNA by IRE1 Is Sequence Specific, Temporally Separate from XBP1 Splicing, and Dispensable for Cell Viability under Acute Endoplasmic Reticulum Stress. Molecular and cellular biology 52 25870107
2017 The TDH-GCN5L1-Fbxo15-KBP axis limits mitochondrial biogenesis in mouse embryonic stem cells. Nature cell biology 45 28319092
2012 The BLOS1-interacting protein KXD1 is involved in the biogenesis of lysosome-related organelles. Traffic (Copenhagen, Denmark) 37 22554196
2022 Mitochondrial GCN5L1 regulates glutaminase acetylation and hepatocellular carcinoma. Clinical and translational medicine 31 35538890
2021 BLOC1S1/GCN5L1/BORCS1 is a critical mediator for the initiation of autolysosomal tubulation. Autophagy 30 33629936
2018 Development of the Swimbladder Surfactant System and Biogenesis of Lysosome-Related Organelles Is Regulated by BLOS1 in Zebrafish. Genetics 30 29339408
2019 Cardiac-specific deletion of GCN5L1 restricts recovery from ischemia-reperfusion injury. Journal of molecular and cellular cardiology 25 30776374
2018 GCN5L1 interacts with αTAT1 and RanBP2 to regulate hepatic α-tubulin acetylation and lysosome trafficking. Journal of cell science 25 30333138
2019 Loss of GCN5L1 in cardiac cells disrupts glucose metabolism and promotes cell death via reduced Akt/mTORC2 signaling. The Biochemical journal 24 31138772
2020 Cardiomyocyte-specific deletion of GCN5L1 in mice restricts mitochondrial protein hyperacetylation in response to a high fat diet. Scientific reports 22 32606301
2022 GCN5L1 impairs diastolic function in mice exposed to a high fat diet by restricting cardiac pyruvate oxidation. Physiological reports 21 35924321
2023 Retrograde regulation of mitochondrial fission and epithelial to mesenchymal transition in hepatocellular carcinoma by GCN5L1. Oncogene 20 36759571
2020 The emerging roles of GCN5L1 in mitochondrial and vacuolar organelle biology. Biochimica et biophysica acta. Gene regulatory mechanisms 20 32599084
1996 Isolation and characterization of a human cDNA clone (GCN5L1) homologous to GCN5, a yeast transcription activator. Cytogenetics and cell genetics 20 8646881
2022 GCN5L1-mediated TFAM acetylation at K76 participates in mitochondrial biogenesis in acute kidney injury. Journal of translational medicine 19 36474281
2024 Mitochondrial GCN5L1 acts as a novel regulator for iron homeostasis to promote sorafenib sensitivity in hepatocellular carcinoma. Journal of translational medicine 15 38918793
2024 Drp1 acetylation mediated by CDK5-AMPK-GCN5L1 axis promotes cerebral ischemic injury via facilitating mitochondrial fission. Molecular medicine (Cambridge, Mass.) 15 39390372
2022 Brucella activates the host RIDD pathway to subvert BLOS1-directed immune defense. eLife 15 35587649
2019 GCN5L1 controls renal lipotoxicity through regulating acetylation of fatty acid oxidation enzymes. Journal of physiology and biochemistry 15 31760589
2024 Loss of GCN5L1 exacerbates damage in alcoholic liver disease through ferroptosis activation. Liver international : official journal of the International Association for the Study of the Liver 14 38597373
1997 Cloning and structural analysis of the murine GCN5L1 gene. Gene 14 9426003
2022 Regulation of Blos1 by IRE1 prevents the accumulation of Huntingtin protein aggregates. Molecular biology of the cell 13 36044348
2022 The endo-lysosomal regulatory protein BLOC1S1 modulates hepatic lysosomal content and lysosomal lipolysis. Biochemical and biophysical research communications 12 36535215
2020 BLOS1 mediates kinesin switch during endosomal recycling of LDL receptor. eLife 12 33179593
2024 Cardiomyocyte-specific deletion of GCN5L1 reduces lysine acetylation and attenuates diastolic dysfunction in aged mice by improving cardiac fatty acid oxidation. The Biochemical journal 10 38390938
2022 GPER-dependent estrogen signaling increases cardiac GCN5L1 expression. American journal of physiology. Heart and circulatory physiology 10 35245133
2019 Loss of GCN5L1 in cardiac cells limits mitochondrial respiratory capacity under hyperglycemic conditions. Physiological reports 9 31033247
2022 Mitochondrial GCN5L1 regulates cytosolic redox state and hepatic gluconeogenesis via glycerol phosphate shuttle GPD2. Biochemical and biophysical research communications 8 35802941
2024 BLOC1S1 Control of Vacuolar Organelle Fidelity Modulates Murine TH2 Cell Immunity and Allergy Susceptibility. Allergy 7 39737471
2024 Zhuangyao Jianshen Wan ameliorates senile osteoporosis in SAMP6 mice through Modulation of the GCN5L1-mediated PI3K/Akt/wnt signaling pathway. Journal of orthopaedic translation 6 39568803
2023 GCN5L1 regulates pulmonary surfactant production by modulating lamellar body biogenesis and trafficking in mouse alveolar epithelial cells. Cellular & molecular biology letters 5 37936104
2025 Mitochondrial GCN5L1 coordinates with YME1L and MICOS to remodel mitochondrial cristae in white adipocytes and modulate obesity. Cell reports 4 40338741
2024 Validation of GCN5L1/BLOC1S1/BLOS1 antibodies using knockout cells and tissue. The Biochemical journal 3 38683688
2022 Generation of human induced pluripotential stem cells from individuals with complex heterozygous, isogenic corrected, and homozygous Bloc1s1 mutations. Stem cell research 3 36070637
2026 Mitochondrial retrograde signal through GCN5L1 transition-mediated PPARγ stabilization promotes MASLD development. JCI insight 2 41574605
2025 GCN5L1 Aggravates Postherpetic Neuralgia Through Regulating Microglial Mitochondrial Fission-Fusion Homeostasis. Journal of cellular and molecular medicine 2 40988108
2025 DL-3-n-Butylphthalide Protects Mitochondria Against Ischemia/Hypoxia Damage via Suppressing GCN5L1-Mediated Drp1 Acetylation in Neurons and Mouse Brains. CNS neuroscience & therapeutics 2 41320852
2024 BLOC1S1 control of vacuolar organelle fidelity modulates TH2 cell immunity and allergy susceptibility. bioRxiv : the preprint server for biology 2 39803487
2026 BLOC1S1 variants cause lysosomal and autophagic defects resulting in a hypomyelinating leukodystrophy with epileptic encephalopathy. American journal of human genetics 1 41887224
2025 BLOC1S1 Attenuates B. Melitensis 16M LPS-Triggered Autophagy by Spatial Confinement of TDP-43. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 40936170
2025 GCN5L1 Inhibits Pyruvate Dehydrogenase Phosphorylation During Cardiac Ischemia-Reperfusion Injury. FASEB bioAdvances 1 40950650
2026 GCN5L1-Mediated Lysine Acetylation Regulates Mitochondrial Bioenergetics and Redox Homeostasis in the Aged Heart. Antioxidants (Basel, Switzerland) 0 42072123
2026 BLOS1 overexpression enhances goat immune response to Brucella LPS through augmented autophagy with associated gut microbiota remodeling. Veterinary journal (London, England : 1997) 0 42162897
2026 BLOC1S1 regulates autolysosomal and exosomal dynamics during CD4⁺ T cell differentiation. bioRxiv : the preprint server for biology 0 42239123
2025 Cardiac-specific GCN5L1 deficiency promotes MASLD in HFpEF. bioRxiv : the preprint server for biology 0 39975261
2025 GCN5L1 inhibits pyruvate dehydrogenase phosphorylation during cardiac ischemia-reperfusion injury. bioRxiv : the preprint server for biology 0 40475660
2025 BLOC1S1 variants cause lysosomal and autophagic defects resulting in a hypomyelinating leukodystrophy with epileptic encephalopathy. medRxiv : the preprint server for health sciences 0 40791729
2025 BLOC1S1 depletion via splice-switching oligonucleotides improves mitochondrial respiration and rescues ALS phenotypes. Molecular therapy : the journal of the American Society of Gene Therapy 0 41383013
2024 GCN5L1-mediated acetylation prevents Rictor degradation in cardiac cells after hypoxic stress. Cellular signalling 0 38281616
2023 Validation of GCN5L1/BLOC1S1/BLOS1 Antibodies Using Knockout Cells and Tissue. bioRxiv : the preprint server for biology 0 37503156
2023 GCN5L1-mediated acetylation prevents Rictor degradation in cardiac cells after hypoxic stress. bioRxiv : the preprint server for biology 0 37961692
2023 [BLOC1S1 promotes proliferation of goat spermatogonial stem cells]. Sheng wu gong cheng xue bao = Chinese journal of biotechnology 0 38147990

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