Affinage

OMA1

Metalloendopeptidase OMA1, mitochondrial · UniProt Q96E52

Length
524 aa
Mass
60.1 kDa
Annotated
2026-04-29
75 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OMA1 is a mitochondrial inner membrane zinc metalloprotease that functions as a stress-responsive quality control hub, integrating signals from membrane depolarization, oxidative stress, and protein misfolding to remodel mitochondrial dynamics, cristae architecture, bioenergetics, and protein import. Under basal conditions OMA1 is largely quiescent, but upon stress it undergoes conformational activation—regulated by redox-sensitive disulfide bonds (Cys272/Cys332 and Cys403), cardiolipin binding, and prohibitin-mediated turnover—and cleaves key substrates including OPA1 at the S1 site (driving mitochondrial fragmentation and cytochrome c release during apoptosis), DELE1 (activating the HRI-eIF2α integrated stress response), AIFM1 (reducing OXPHOS capacity), DNAJC15 (restricting mitochondrial protein import), and arrested translocase intermediates, while also degrading misfolded inner membrane proteins (PMID:12963738, PMID:20038677, PMID:32132707, PMID:41876740, PMID:41760807, PMID:38530280). OMA1 activation is coupled to its own autocatalytic degradation, ensuring reversibility of the stress response, and is positioned downstream of Bax/Bak oligomerization in apoptosis and upstream of PINK1 stabilization in mitophagy, with OMA1-mediated PINK1 degradation counterbalanced by TIM23-dependent protection (PMID:24550258, PMID:25275009, PMID:30733118, PMID:37160114). OMA1 cooperates with Parkin to maintain mitochondrial fusion and genome integrity under physiological conditions; combined loss of both causes severe organismal phenotypes including premature death and innate immune activation, while individual loss of OMA1 in mice causes obesity and impaired thermogenesis through persistent OPA1-dependent hyperfusion (PMID:39972141, PMID:22433842).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2003 High

    The foundational question of whether mitochondria possess an ATP-independent inner membrane quality control protease was answered by identification of Oma1 as a metallopeptidase that degrades misfolded membrane proteins like Oxa1 derivatives, establishing a new proteolytic pathway distinct from m-AAA protease function.

    Evidence Biochemical fractionation, in vitro protease assays, and cleavage-site mapping of Oxa1 substrate in yeast

    PMID:12963738

    Open questions at the time
    • Mammalian substrate specificity unknown
    • No structural information on OMA1
    • Relationship to mitochondrial dynamics not yet explored
  2. 2009 High

    The critical question of which protease mediates stress-induced OPA1 processing was resolved: OMA1 cleaves OPA1 at the S1 site upon loss of membrane potential, converting long fusion-competent OPA1 to short forms and inhibiting mitochondrial fusion, while constitutive OPA1 processing depends on m-AAA proteases—establishing OMA1 as the stress-responsive arm of OPA1 regulation.

    Evidence siRNA knockdown in mammalian cells, OPA1 isoform Western blot, mitochondrial morphology imaging, CCCP/oligomycin treatment, replicated across two independent laboratories

    PMID:20038677 PMID:20038678

    Open questions at the time
    • Mechanism of OMA1 activation by stress unknown
    • In vivo physiological relevance not yet tested
    • Whether OMA1 has substrates beyond OPA1 unclear
  3. 2012 High

    The physiological relevance of OMA1 was established in vivo: OMA1-knockout mice showed that loss of stress-induced OPA1 processing causes persistent mitochondrial hyperfusion leading to obesity, hepatic steatosis, and impaired thermogenesis, demonstrating OMA1 is essential for metabolic homeostasis.

    Evidence Oma1 knockout mice with comprehensive metabolic phenotyping, high-fat diet challenge, OPA1 isoform analysis

    PMID:22433842

    Open questions at the time
    • Whether metabolic phenotype is entirely OPA1-dependent or involves other substrates unknown
    • Tissue-specific requirements of OMA1 not dissected
  4. 2014 High

    Multiple advances resolved how OMA1 is activated and regulated, and positioned it in the apoptotic cascade: OMA1 possesses an N-terminal stress-sensor domain and undergoes autocatalytic self-degradation ensuring reversibility; its C-terminal domain mediates stress-responsive oligomeric conformational changes; Bax/Bak oligomerization activates OMA1 upstream of cristae remodeling and cytochrome c release; and OMA1-generated short OPA1 forms promote fission at ER-mitochondria contact sites.

    Evidence Domain mutagenesis, native gel electrophoresis, pulse-chase degradation, inducible Bim/tBid expression, OMA1 KO/KD with cytochrome c release assays, YME1L/OMA1 double-knockout epistasis, electron microscopy, ischemia-reperfusion kidney injury model

    PMID:24550258 PMID:24616225 PMID:24648523 PMID:24671334 PMID:25275009

    Open questions at the time
    • Molecular details of how Bax/Bak signal reaches OMA1 unclear
    • Whether autocatalytic degradation occurs in trans or cis unknown
    • Structural basis of stress-sensor domain function unresolved
  5. 2019 High

    Three regulatory layers of OMA1 were uncovered: OMA1 activity is tuned by redox-sensitive IMS-exposed disulfide bonds (Cys272/Cys332); prohibitin scaffolds and cardiolipin binding promote OMA1 turnover to limit its activity; and OMA1 degrades imported PINK1 in depolarized mitochondria, opposing Tom7-mediated PINK1 stabilization—linking OMA1 to PINK1/Parkin mitophagy signaling.

    Evidence Cysteine mutagenesis with redox state analysis in yeast and mammalian cells; PHB2-KO neurons with cardiolipin-binding domain deletions and turnover assays; Tom7/OMA1 KO epistasis with PINK1 import and Parkinson's-relevant mutant rescue

    PMID:30733118 PMID:31044600 PMID:31819158

    Open questions at the time
    • How cardiolipin binding mechanistically promotes OMA1 turnover is unclear
    • Relative contribution of redox versus depolarization sensing in vivo not quantified
    • Whether OMA1-PINK1 regulation is tissue-specific unknown
  6. 2020 High

    A genome-wide screen revealed that OMA1 relays mitochondrial stress to the cytosol by cleaving DELE1, whose released fragment activates the eIF2α kinase HRI to induce the integrated stress response and ATF4 translation—establishing the OMA1-DELE1-HRI pathway as a mitochondria-to-nucleus stress signaling axis.

    Evidence Genome-wide CRISPRi screen, OMA1/DELE1/HRI knockdown, DELE1-HRI co-immunoprecipitation, eIF2α phosphorylation and ATF4 reporter assays

    PMID:32132707

    Open questions at the time
    • Full spectrum of ISR target genes activated by this pathway not catalogued
    • Whether OMA1-DELE1-HRI operates in all tissues equally unknown
    • Structural basis of DELE1 cleavage site recognition unresolved
  7. 2022 High

    The in vivo survival function of OMA1's dual signaling was demonstrated: in CHCHD10 mitochondrial myopathy mice, OMA1 coordinates both local fragmentation and global ISR activation via DELE1, and OMA1-dependent responses are essential for neonatal survival under inner membrane stress.

    Evidence CHCHD10 knock-in mouse model crossed with OMA1 KO, DELE1 cleavage assays, survival analysis, mitochondrial morphology

    PMID:35700042

    Open questions at the time
    • Whether pharmacological OMA1 modulation can rescue CHCHD10 disease unknown
    • Relative contribution of OPA1 versus DELE1 cleavage to survival not separated
  8. 2023 Medium

    Additional regulatory and functional dimensions were defined: mammalian Cys403 acts as a redox switch controlling OMA1 stress responses; TIM23 physically protects PINK1 from OMA1-mediated degradation; and OMA1 protects against DNA damage-induced apoptosis through metabolic control of glycolysis independent of OPA1 or DELE1.

    Evidence Prime editing of C403A in mouse cells with mitochondrial stress/apoptosis assays; PINK1 co-IP mass spectrometry with TIM23 KD and OMA1 KO epistasis; CRISPR metabolism screen with metabolic flux analysis in OMA1-KO cells

    PMID:37002921 PMID:37024121 PMID:37160114

    Open questions at the time
    • Whether C403 redox sensing is mechanistically linked to the Cys272/Cys332 disulfide is unknown
    • Glycolysis-regulatory substrate of OMA1 not identified
    • Structural basis of TIM23-PINK1 protection from OMA1 unclear
  9. 2024 High

    OMA1's substrate repertoire was expanded to include arrested translocase import intermediates, which OMA1 cleaves upon depolarization to unclog the TIM23 channel, with released fragments cleared by cytosolic VCP/p97 and the proteasome—revealing OMA1 as a translocase rescue factor.

    Evidence Translocase clogging cell model, OMA1 KO/KD, cleavage fragment analysis, VCP/proteasome inhibitor epistasis

    PMID:38530280

    Open questions at the time
    • How OMA1 accesses substrates stuck in the translocase channel is structurally unresolved
    • Scope of physiological import intermediates cleaved by OMA1 not determined
  10. 2025 High

    Systematic genetic epistasis across 18 mouse models revealed that Parkin and OMA1 constitute a dual regulatory system safeguarding mitochondrial fusion and genome integrity through MFN1 and OPA1 respectively; combined loss causes severe organismal defects including premature death and innate immune activation, while individual loss is tolerated.

    Evidence 18 single/double/triple whole-body and tissue-specific KO mice, metabolomics, RNA sequencing

    PMID:39972141

    Open questions at the time
    • Whether Parkin-OMA1 cooperation involves direct physical interaction unknown
    • Mechanism linking combined loss to innate immune activation not fully defined
  11. 2026 High

    Two new OMA1 substrates were identified that expand its role beyond dynamics: OMA1 cleaves AIFM1 in the IMS with slower kinetics than OPA1, reducing OXPHOS by dislocating AIFM1 from respiratory complexes; and OMA1 cleaves the mitochondrial chaperone DNAJC15, whose subsequent degradation by AFG3L2 restricts protein import and OXPHOS biogenesis under stress, with non-imported preproteins triggering ER UPR.

    Evidence In vitro cleavage reconstitution, multiproteomic approaches, OMA1 KO, co-IP of AIFM1 with OXPHOS subunits, mitochondrial import assays, ER stress reporters

    PMID:41760807 PMID:41876740

    Open questions at the time
    • Complete substrate degradome of OMA1 not yet defined
    • How OMA1 achieves differential cleavage kinetics between substrates is structurally unclear
    • Whether AIFM1 and DNAJC15 cleavage are relevant in vivo in specific tissues not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic structure of OMA1 and how it achieves substrate selectivity, the full in vivo substrate repertoire, whether the glycolysis-protective function involves an unidentified substrate, and whether pharmacological modulation of OMA1 is therapeutically tractable in mitochondrial diseases or neurodegeneration.
  • No crystal or cryo-EM structure of OMA1 exists
  • Complete degradome not catalogued by unbiased proteomics
  • Therapeutic targeting not explored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016787 hydrolase activity 4 GO:0140299 molecular sensor activity 3 GO:0008289 lipid binding 1
Localization
GO:0005739 mitochondrion 5
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1430728 Metabolism 2 R-HSA-9612973 Autophagy 2
Partners
AIFM1DELE1DNAJC15HSPA9MIC60OPA1PHB2PINK1
Complex memberships
OMA1 homo-oligomeric complexOMA1-MICOS complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 OMA1 (Oma1) is a novel conserved metallopeptidase embedded in the mitochondrial inner membrane that degrades misfolded membrane proteins (e.g., a misfolded derivative of Oxa1) in an ATP-independent manner, with its proteolytic center exposed to the matrix side; it was identified as a component of the mitochondrial inner membrane quality control system overlapping with the m-AAA protease. Biochemical fractionation, in vitro protease assays, cleavage-site mapping of Oxa1 substrate in yeast The Journal of biological chemistry High 12963738
2009 OMA1 mediates stress-induced (loss of membrane potential or ATP) proteolytic cleavage of OPA1 at the S1 site in mammalian cells, converting long OPA1 isoforms to short isoforms and inhibiting mitochondrial fusion; siRNA knockdown of OMA1 inhibits this inducible cleavage, retains fusion competence, and slows apoptosis. OMA1 itself is normally processed from 60 kDa to 40 kDa, and loss of membrane potential causes 60-kDa OMA1 to accumulate, suggesting OMA1 activity is attenuated by proteolytic degradation. siRNA knockdown, Western blot for OPA1 isoforms, live-cell imaging of mitochondrial morphology, CCCP/oligomycin treatment The Journal of cell biology High 20038677 20038678
2009 Two classes of metallopeptidases regulate OPA1 cleavage in the mitochondrial inner membrane: isoenzymes of the m-AAA protease (paraplegin, AFG3L1, AFG3L2) for constitutive processing, and the ATP-independent OMA1 for stress-induced processing. Loss of AFG3L2 or mitochondrial DNA depletion induces OPA1 processing specifically by OMA1, linking distinct peptidases to constitutive versus induced OPA1 cleavage. Knockout/knockdown of AFG3L1/2, dominant-negative AFG3L2 expression, siRNA, Western blot for OPA1 isoforms, electron microscopy The Journal of cell biology High 20038678
2012 In vivo, OMA1 deficiency in mice prevents stress-induced OPA1 proteolytic inactivation, causing a persistent mitochondrial fusion/fission imbalance that results in obesity, hepatic steatosis, decreased energy expenditure, and impaired thermogenesis, establishing OMA1 as essential for metabolic homeostasis via OPA1 regulation. Oma1 knockout mice, metabolic phenotyping, Western blot for OPA1 isoforms, transcriptional profiling, high-fat diet challenge The EMBO journal High 22433842
2014 YME1L and OMA1 cleave OPA1 at two distinct sites (S2 and S1, respectively) to balance mitochondrial fusion and fission. Long OPA1 forms are sufficient for mitochondrial fusion; short OPA1 forms (generated by OMA1) promote fission and partially colocalize with ER-mitochondria contact sites and the mitochondrial fission machinery. Deletion of OMA1 rescued mitochondrial tubulation, cristae morphogenesis, and apoptotic resistance in YME1L-null cells. YME1L/OMA1 double knockout cells, mitochondrial morphology imaging, electron microscopy, apoptosis assays, expression of GTPase-inactive short OPA1 The Journal of cell biology High 24616225
2014 OMA1 is constitutively active but undergoes strongly enhanced proteolytic activity in response to various stress insults (mitochondrial depolarization, heat, oxidative stress). An N-terminal stress-sensor domain (present only in higher eukaryotes) modulates OMA1 activation. OMA1 activation is coupled to its own autocatalytic degradation initiating from both termini, ensuring reversibility of the stress response and allowing OPA1-mediated fusion to resume upon stress alleviation. OMA1 truncation/domain mutant analysis, in-cell stress assays, Western blot for OMA1 and OPA1 isoforms, pulse-chase degradation experiments The EMBO journal High 24550258
2014 Oligomerized Bax and Bak activate OMA1 in a Bax/Bak-dependent fashion during apoptosis; activated OMA1 then cleaves OPA1, which is critical for mitochondrial cristae remodeling. Knockdown or knockout of OMA1 attenuates cytochrome c release, placing OMA1 downstream of Bax/Bak oligomerization in the apoptotic pathway. Inducible Bim/tBid expression cell lines, OMA1 siRNA/KO, cytochrome c release assays, Western blot for OPA1 isoforms Proceedings of the National Academy of Sciences of the United States of America High 25275009
2014 OMA1-mediated OPA1 proteolysis plays a critical role in mitochondrial fragmentation and apoptosis during ischemic acute kidney injury. OMA1 knockdown in renal tubular cells suppressed OPA1 cleavage, mitochondrial fragmentation, cytochrome c release, and apoptosis; OMA1-deficient mice were protected from ischemic AKI with better renal function and less tubular damage. OMA1 siRNA knockdown in proximal tubular cells, OMA1 knockout mice, ischemia-reperfusion model, Western blot, mitochondrial morphology imaging, renal function assays American journal of physiology. Renal physiology High 24671334
2014 Stress-triggered activation of OMA1 (Oma1) involves conformational changes within its homo-oligomeric complex associated with C-terminal residues. Substitutions in the conserved C-terminal region impair formation of the labile proteolytically active complex in response to stress stimuli. OMA1 genetically interacts with other inner membrane-bound quality control proteases in yeast. Oma1 C-terminal mutagenesis in yeast, native gel electrophoresis of Oma1 complexes, protease activity assays, genetic interaction screens The Journal of biological chemistry Medium 24648523
2019 PINK1 import into depolarized mitochondria can be cleaved and degraded by the OMA1 protease when PINK1 fails to arrest at the outer mitochondrial membrane. Tom7 and OMA1 exert opposing ('tug-of-war') effects on PINK1 accumulation: deletion of Tom7 allows PINK1 import into depolarized mitochondria where it is cleaved by OMA1, while OMA1 suppression rescues defective import arrest seen with certain Parkinson's disease PINK1 mutations. Tom7/OMA1 siRNA and KO, PINK1 import assays, PINK1 mutant rescue experiments, Western blot for PINK1 cleavage Molecular cell High 30733118
2019 Prohibitin (PHB1/PHB2) promotes OMA1 turnover in neurons, effectively decreasing the pool of active OMA1. OMA1 binds to cardiolipin (CL), a major mitochondrial phospholipid, and CL binding promotes OMA1 turnover; deletion of the CL-binding domain of OMA1 decreases its turnover rate. This PHB-mediated CL stabilization regulates OMA1 activity and downstream cytochrome c release. PHB2 KO neurons, OMA1 domain deletion mutants, cardiolipin-binding assays, OMA1 turnover pulse-chase experiments, cytochrome c release assays, caspase activation Cell death and differentiation High 31819158
2019 Oma1 is a redox-dependent protein existing in a semi-oxidized state. Two IMS-exposed conserved cysteine residues (Cys272 and Cys332) form a disulfide bond that plays a structural role influencing conformational stability and proteolytic activity of the Oma1 oligomeric complex. Reduction/oxidation of these residues dynamically tunes Oma1 activity and stability in both yeast and mammalian mitochondria. Cysteine mutagenesis, redox state analysis by alkylation/gel-shift, in vitro substrate engagement assays, genetic validation in yeast Antioxidants & redox signaling High 31044600
2020 Mitochondrial stress activates OMA1-dependent cleavage of DELE1, releasing a short DELE1 fragment that accumulates in the cytosol where it interacts with and activates the eIF2α kinase HRI, thereby phosphorylating eIF2α and inducing ATF4 translation—constituting the OMA1-DELE1-HRI pathway that relays mitochondrial stress to the integrated stress response. Genome-wide CRISPRi screen, OMA1/DELE1/HRI knockdown, DELE1 cleavage assays, co-immunoprecipitation of DELE1 with HRI, eIF2α phosphorylation measurement, ATF4 reporter assays Nature High 32132707
2020 Loss of both CHCHD2 and CHCHD10 activates OMA1, which cleaves L-OPA1, causing disrupted mitochondrial cristae. OMA1 activation similarly occurs in affected tissues of mutant CHCHD10 knock-in mice. Partial functional redundancy between CHCHD2 and CHCHD10 was demonstrated using OMA1 activation as a functional assay. CHCHD2/CHCHD10 double-knockout mice, CHCHD10 knock-in mice, OMA1 activity/OPA1 cleavage assays, electron microscopy, cardiomyopathy phenotyping Human molecular genetics High 32338760
2021 OMA1 associates dynamically with the MICOS complex via the subunit MIC60, independently of OPA1. This OMA1-MICOS association is required for stability of MICOS and intermembrane contacts, as well as for optimal bioenergetic output and apoptosis. Loss of OMA1 disrupts these activities, which can be alleviated by a MICOS-emulating intermembrane bridge. Co-immunoprecipitation of OMA1 with MICOS subunits, OMA1 KO cells, bioenergetics assays, synthetic rescue with intermembrane bridge construct iScience Medium 33644718
2022 In CHCHD10 mitochondrial myopathy, OMA1 mediates a coordinated local and global stress response: locally, OMA1 drives mitochondrial fragmentation; globally, OMA1 cleaves DELE1 to activate the integrated stress response. OMA1-dependent survival was essential for neonatal survival in CHCHD10-KI mice conditionally under inner mitochondrial membrane stress. CHCHD10 knock-in mouse model, OMA1 KO crosses, DELE1 cleavage assays, mitochondrial morphology, survival analysis, isoform profiling The Journal of clinical investigation High 35700042
2023 TIM23 forms a physical complex with PINK1 and facilitates PINK1 accumulation by protecting it from OMA1-mediated degradation upon mitochondrial depolarization. Inactivation of OMA1 enhances PINK1 accumulation and compensates for TIM23 downregulation, and rescues defects in pathogenic PINK1 mutants that fail to interact with TIM23. Mass spectrometry of PINK1 co-immunoprecipitates, TIM23 knockdown, OMA1 KO, PINK1 autophosphorylation assays, PINK1 mutant rescue experiments Cell reports High 37160114
2023 Mitochondrial cysteine 403 of OMA1 constitutes a redox-sensing site in mammalian cells. Prime editing of OMA1 C403A in mouse sarcoma cells impaired mitochondrial stress responses including ATP production, mitochondrial fission, and apoptosis, and enhanced mitochondrial DNA release, demonstrating a functional redox switch. Prime editing (C403A mutation), mitochondrial stress assays, mitochondrial DNA release measurement, apoptosis assays, immunocompetent tumor models Life science alliance Medium 37024121
2023 OMA1 protects against DNA damage-induced apoptosis through metabolic control of glycolysis rather than through OPA1 or DELE1 processing. OMA1-deficient cells show reduced glycolysis and accumulate OXPHOS proteins upon DNA damage; OXPHOS inhibition restores glycolysis and resistance to DNA damage. CRISPR screen (metabolism-focused), OMA1 KO cells, metabolic flux assays, OXPHOS inhibitor rescue, apoptosis assays Cell reports Medium 37002921
2024 OMA1 cleaves arrested import intermediates in the mitochondrial translocase upon mitochondrial membrane depolarization in human cells, releasing the stalled protein fragment from the translocase channel. The released fragment is subsequently cleared in the cytosol by VCP/p97 and the proteasome. Translocase clogging cell model, OMA1 KO/KD, Western blot for cleavage fragments, VCP/proteasome inhibitors The Journal of cell biology High 38530280
2024 OMA1-dependent OPA1 processing is sensitive to both mitochondrial membrane potential depolarization and oxidative stress in neuronal cells; oxidative stress is necessary for depolarization-induced OMA1-mediated proteolysis. OMA1 KO cells show exacerbated acute mitochondrial fragmentation but better restorative fusion after stress due to preserved L-OPA1. OMA1 KO HT22 cells, mitochondrial morphology imaging, ROS measurement, oxygen-glucose deprivation/reoxygenation model, OPA1 isoform Western blot FASEB journal Medium 39312414
2025 Parkin (ubiquitin E3 ligase) and OMA1 (metalloprotease) constitute a dual regulatory system that safeguards mitochondrial structure and genome via mitochondrial fusion mediated by MFN1 (outer membrane) and OPA1 (inner membrane). Individual loss of Parkin or OMA1 does not affect mitochondrial integrity, but combined loss causes small body size, low locomotor activity, premature death, mitochondrial abnormalities, and innate immune responses. 18 single/double/triple whole-body and tissue-specific KO and mutant mice, mitochondrial morphology analysis, untargeted metabolomics, RNA sequencing Nature High 39972141
2026 OMA1 cleaves AIFM1 (AIF/apoptosis-inducing factor) in the intermembrane space under mitochondrial stress conditions, with slower kinetics than OPA1 cleavage. This OMA1-mediated AIFM1 dislocation from the inner membrane reduces AIFM1 interactions with OXPHOS subunits, decreasing respiratory activity and impairing cell growth. Under steady-state conditions, AIFM1 broadly mediates import of respiratory complex I subunits via the TIM23 complex. In vitro and in vivo multiproteomic approaches, biochemical cleavage assays, OMA1 KO, co-immunoprecipitation of AIFM1 with OXPHOS subunits, respiratory activity measurement, mitochondrial protein import assays The EMBO journal High 41876740
2026 OMA1 cleaves the mitochondrial chaperone DNAJC15, promoting its degradation by the m-AAA protease AFG3L2 under cellular stress. Loss of DNAJC15 impairs mitochondrial protein import and restricts OXPHOS biogenesis under conditions of mitochondrial dysfunction; non-imported preproteins accumulate at the ER, inducing an unfolded protein response. OMA1 KO, DNAJC15 cleavage assays, m-AAA protease interaction experiments, mitochondrial protein import assays, OXPHOS biogenesis quantification, ER stress reporters Nature structural & molecular biology High 41760807
2018 Leptin-mediated protection of mitochondrial integrity in mesenchymal stem cells requires GSK3 phosphorylation as a prerequisite for ubiquitination-dependent proteasomal degradation of OMA1, thereby attenuating OMA1-mediated OPA1 cleavage. The proteasome inhibitor MG132 prevented leptin-induced OMA1 degradation, and GSK3 inhibitor (SB216763) also reduced OMA1 levels. Leptin treatment of hMSCs, MG132/GSK3 inhibitor treatment, OMA1/OPA1 Western blot, OPA1 siRNA rescue, mitochondrial morphology imaging Cell death & disease Medium 29748581
2019 OMA1 links mitochondrial protein quality control to TOR signaling in yeast: inactivation of Oma1 leads to enhanced ROS production during logarithmic growth and reduced stress signaling via the TORC1-Rim15-Msn2/Msn4 axis. Pharmacological or genetic ROS prevention in Oma1-deficient cells restores defective TOR signaling. Oma1 KO yeast, ROS measurement, genetic epistasis with TORC1 pathway components, pharmacological ROS inhibition Molecular and cellular biology Medium 27325672
2024 OMA1 competitively binds to HSPA9 in glioblastoma cells, inducing mitophagy and promoting cGAS-STING activation through increased mitochondrial DNA release, which upregulates PD-L1 transcription and contributes to immune evasion. Co-immunoprecipitation, mass spectrometry, immunofluorescence, OMA1 KD, cGAS-STING pathway assays, PD-L1 measurement Journal for immunotherapy of cancer Medium 38604814

Source papers

Stage 0 corpus · 75 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission. The Journal of cell biology 644 24616225
2020 Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway. Nature 504 32132707
2009 Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1. The Journal of cell biology 476 20038678
2009 Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells. The Journal of cell biology 413 20038677
2014 Stress-induced OMA1 activation and autocatalytic turnover regulate OPA1-dependent mitochondrial dynamics. The EMBO journal 275 24550258
2012 Loss of mitochondrial protease OMA1 alters processing of the GTPase OPA1 and causes obesity and defective thermogenesis in mice. The EMBO journal 225 22433842
2014 Activation of mitochondrial protease OMA1 by Bax and Bak promotes cytochrome c release during apoptosis. Proceedings of the National Academy of Sciences of the United States of America 181 25275009
2001 Two zinc finger proteins, OMA-1 and OMA-2, are redundantly required for oocyte maturation in C. elegans. Developmental cell 152 11702779
2019 Reciprocal Roles of Tom7 and OMA1 during Mitochondrial Import and Activation of PINK1. Molecular cell 138 30733118
2003 Oma1, a novel membrane-bound metallopeptidase in mitochondria with activities overlapping with the m-AAA protease. The Journal of biological chemistry 125 12963738
2021 Mitochondrial OMA1 and OPA1 as Gatekeepers of Organellar Structure/Function and Cellular Stress Response. Frontiers in cell and developmental biology 107 33842456
2014 OMA1 mediates OPA1 proteolysis and mitochondrial fragmentation in experimental models of ischemic kidney injury. American journal of physiology. Renal physiology 98 24671334
2005 The Conserved Kinases CDK-1, GSK-3, KIN-19, and MBK-2 Promote OMA-1 Destruction to Regulate the Oocyte-to-Embryo Transition in C. elegans. Current biology : CB 89 16343905
2014 p53 is required for cisplatin-induced processing of the mitochondrial fusion protein L-Opa1 that is mediated by the mitochondrial metallopeptidase Oma1 in gynecologic cancers. The Journal of biological chemistry 83 25112877
2005 DYRK2 and GSK-3 phosphorylate and promote the timely degradation of OMA-1, a key regulator of the oocyte-to-embryo transition in C. elegans. Developmental biology 80 16289132
2003 A gain-of-function mutation in oma-1, a C. elegans gene required for oocyte maturation, results in delayed degradation of maternal proteins and embryonic lethality. Developmental biology 69 12781695
2020 Loss of CHCHD2 and CHCHD10 activates OMA1 peptidase to disrupt mitochondrial cristae phenocopying patient mutations. Human molecular genetics 63 32338760
2019 Prohibitin levels regulate OMA1 activity and turnover in neurons. Cell death and differentiation 57 31819158
2018 Leptin increases mitochondrial OPA1 via GSK3-mediated OMA1 ubiquitination to enhance therapeutic effects of mesenchymal stem cell transplantation. Cell death & disease 55 29748581
2022 OMA1 mediates local and global stress responses against protein misfolding in CHCHD10 mitochondrial myopathy. The Journal of clinical investigation 53 35700042
2016 A threshold of transmembrane potential is required for mitochondrial dynamic balance mediated by DRP1 and OMA1. Cellular and molecular life sciences : CMLS 47 27858084
2014 Stress-triggered activation of the metalloprotease Oma1 involves its C-terminal region and is important for mitochondrial stress protection in yeast. The Journal of biological chemistry 45 24648523
2019 EGCG protects cardiomyocytes against hypoxia-reperfusion injury through inhibition of OMA1 activation. Journal of cell science 43 30518622
2023 TIM23 facilitates PINK1 activation by safeguarding against OMA1-mediated degradation in damaged mitochondria. Cell reports 36 37160114
2021 Protease OMA1 modulates mitochondrial bioenergetics and ultrastructure through dynamic association with MICOS complex. iScience 33 33644718
2020 p32/C1QBP regulates OMA1-dependent proteolytic processing of OPA1 to maintain mitochondrial connectivity related to mitochondrial dysfunction and apoptosis. Scientific reports 32 32606429
2022 The Mitochondrial PHB2/OMA1/DELE1 Pathway Cooperates with Endoplasmic Reticulum Stress to Facilitate the Response to Chemotherapeutics in Ovarian Cancer. International journal of molecular sciences 30 35163244
2018 Selective killing of human T-ALL cells: an integrated approach targeting redox homeostasis and the OMA1/OPA1 axis. Cell death & disease 30 30069011
2024 OMA1 competitively binds to HSPA9 to promote mitophagy and activate the cGAS-STING pathway to mediate GBM immune escape. Journal for immunotherapy of cancer 29 38604814
2019 Targeted OMA1 therapies for cancer. International journal of cancer 29 30714136
2025 Dual regulation of mitochondrial fusion by Parkin-PINK1 and OMA1. Nature 27 39972141
2013 RNA recognition by the Caenorhabditis elegans oocyte maturation determinant OMA-1. The Journal of biological chemistry 27 24014033
2024 OMA1 protease eliminates arrested protein import intermediates upon mitochondrial depolarization. The Journal of cell biology 26 38530280
2024 Mitochondrial membrane potential and oxidative stress interact to regulate Oma1-dependent processing of Opa1 and mitochondrial dynamics. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 39312414
2021 FTSH4 and OMA1 mitochondrial proteases reduce moderate heat stress-induced protein aggregation. Plant physiology 25 34608962
2006 OMA-1 is a P granules-associated protein that is required for germline specification in Caenorhabditis elegans embryos. Genes to cells : devoted to molecular & cellular mechanisms 25 16611242
2019 Pathogenic variants in the AFG3L2 proteolytic domain cause SCA28 through haploinsufficiency and proteostatic stress-driven OMA1 activation. Journal of medical genetics 24 30910913
2019 Depletion of mitochondrial protease OMA1 alters proliferative properties and promotes metastatic growth of breast cancer cells. Scientific reports 21 31611601
2019 Redox Regulation of the Mitochondrial Quality Control Protease Oma1. Antioxidants & redox signaling 19 31044600
2016 Oma1 Links Mitochondrial Protein Quality Control and TOR Signaling To Modulate Physiological Plasticity and Cellular Stress Responses. Molecular and cellular biology 19 27325672
2023 The mitochondrial protease OMA1 acts as a metabolic safeguard upon nuclear DNA damage. Cell reports 18 37002921
2020 OMA1-An integral membrane protease? Biochimica et biophysica acta. Proteins and proteomics 18 33130089
2020 A novel AFG3L2 mutation close to AAA domain leads to aberrant OMA1 and OPA1 processing in a family with optic atrophy. Acta neuropathologica communications 16 32600459
2022 Increased Mobile Zinc Regulates Retinal Ganglion Cell Survival via Activating Mitochondrial OMA1 and Integrated Stress Response. Antioxidants (Basel, Switzerland) 14 36290724
2019 The first direct activity assay for the mitochondrial protease OMA1. Mitochondrion 14 30926535
2024 Sustained OMA1-mediated integrated stress response is beneficial for spastic ataxia type 5. Brain : a journal of neurology 11 37804316
2024 OMA1-Mediated Mitochondrial Dynamics Balance Organellar Homeostasis Upstream of Cellular Stress Responses. International journal of molecular sciences 11 38674151
2024 Inhibition of mitochondrial OMA1 ameliorates osteosarcoma tumorigenesis. Cell death & disease 10 39487118
2023 Targeting Aggressive B-cell Lymphomas through Pharmacological Activation of the Mitochondrial Protease OMA1. Molecular cancer therapeutics 9 37643767
2021 Circular RNA OMA1 regulates the progression of breast cancer via modulation of the miR‑1276/SIRT4 axis. Molecular medicine reports 9 34414449
2022 Recent advances in, and challenges of, designing OMA1 drug screens. Pharmacological research 8 34999225
2013 New roles for OMA1 metalloprotease: From mitochondrial proteostasis to metabolic homeostasis. Adipocyte 7 23700547
2024 Melatonin Rescues Influenza A Virus-Induced Cellular Energy Exhaustion via OMA1-OPA1-S in Acute Exacerbation of COPD. Journal of pineal research 6 39039850
2023 Long Noncoding RNA PCGEM1 Facilitates Tumor Growth and Metastasis of Osteosarcoma by Sponging miR-433-3p and Targeting OMA1. Orthopaedic surgery 6 36782343
2023 An OMA1 redox site controls mitochondrial homeostasis, sarcoma growth, and immunogenicity. Life science alliance 6 37024121
2019 How did a duplicated gene copy evolve into a restorer-of-fertility gene in a plant? The case of Oma1. Royal Society open science 6 31827833
2025 Reduced Expression of UPRmt Proteins HSP10, HSP60, HTRA2, OMA1, SPG7, and YME1L Is Associated with Accelerated Heart Failure in Humans. Biomedicines 5 40426970
2023 Loss of UCP2 causes mitochondrial fragmentation by OMA1-dependent proteolytic processing of OPA1 in podocytes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 4 37874273
2021 OMA1 High-Throughput Screen Reveals Protease Activation by Kinase Inhibitors. ACS chemical biology 4 34672515
2021 The APC/CFZY-1/Cdc20 Complex Coordinates With OMA-1 to Regulate the Oocyte-to-Embryo Transition in Caenorhabditis elegans. Frontiers in cell and developmental biology 4 34722532
2020 A Lineage-Specific Paralog of Oma1 Evolved into a Gene Family from Which a Suppressor of Male Sterility-Inducing Mitochondria Emerged in Plants. Genome biology and evolution 4 32853350
2023 OMA1 and YME1L as a Diagnostic Panel in Hepatocellular Carcinoma. The Yale journal of biology and medicine 3 38161580
2021 Fluorescence-Based Assay For Measuring OMA1 Activity. Methods in molecular biology (Clifton, N.J.) 3 34060052
2025 Mechanism underlying the role of the circRNA OMA1/miR-654-3p/RAF1 axis in children with inflammatory bowel disease. Cytotechnology 2 39867828
2024 The contributory role of GSK3β in hypertension exacerbating atherosclerosis by regulating the OMA1/PGC1α pathway. Apoptosis : an international journal on programmed cell death 2 39427090
2025 Qingyihuaji formula reprograms metabolism to suppress pancreatic cancer growth and progression through LINC00346-OMA1-ATF4 signaling. Journal of ethnopharmacology 1 40294662
2025 Cancer cells surviving cisplatin chemotherapy increase stress-induced OMA1 activity and mitochondrial fragmentation. bioRxiv : the preprint server for biology 1 41256627
2025 Trifloxystrobin induces oxidative stress-dependent activation of the OMA1-DELE1-HRI integrated stress response leading to apoptosis in human neuroblastoma cells. Environmental pollution (Barking, Essex : 1987) 1 41422903
2021 Overexpression of MnSOD Protects against Cold Storage-Induced Mitochondrial Injury but Not against OMA1-Dependent OPA1 Proteolytic Processing in Rat Renal Proximal Tubular Cells. Antioxidants (Basel, Switzerland) 1 34439520
2026 Cancer cells surviving cisplatin chemotherapy increase stress-induced OMA1 activity and mitochondrial fragmentation. Scientific reports 0 41495249
2026 Stress adaptation of mitochondrial protein import by OMA1-mediated degradation of DNAJC15. Nature structural & molecular biology 0 41760807
2026 Stress-induced OMA1-mediated cleavage of AIFM1 suppresses cell growth by controlling mitochondrial OXPHOS activity. The EMBO journal 0 41876740
2025 A conserved triple arginine motif in OMA-1 is required for RNA-binding activity and embryo viability. bioRxiv : the preprint server for biology 0 40463014
2025 A conserved triple arginine motif in OMA-1 is required for RNA-binding activity and embryo viability. RNA (New York, N.Y.) 0 40866298
2025 Niujiaodihuang Detoxify Decoction Inhibits D-GalN/LPS-induced Hepatocyte Ferroptosis by Maintaining Mitochondrial Homeostasis Via OMA1-OPA1 Pathway. Journal of physiological investigation 0 40908818