OMA1 protects from liver injury and tumorigenesis during aging by controlling hepatic immunogenicity
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE283516 | GEO | 2026/05/27
REPOSITORIES: GEO
Similar Datasets
Project description:Heart failure (HF) is a major health and economic burden in developed countries. It has been proposed that the pathogenesis of HF may involve the action of mitochondria. Here we evaluate three different models of HF: tachycardiomyopathy, HF with preserved left ventricular (LV) ejection fraction, and LV myocardial ischemia and hypertrophy. Regardless of whether LVEF is preserved or reduced, our results indicate that the three models share common molecular features: an increase in mitochondrial ROS, followed by ultrastructural alterations in the mitochondrial cristae and loss of mitochondrial integrity that lead to cardiomyocyte death. We show that the ablation of the mitochondrial protease OMA1 averts cardiomyocyte death in all three experimental HF models, and thus, plays a direct role in cardiomyocyte protection. This finding identifies OMA1 as a potential target for preventing the progression of myocardial damage in HF associated to a variety of etiologies.
2018-03-09 | GSE96057 | GEO
Project description:EMBOJ-2024-119185R-Q OMA1 protects from liver injury
2026-06-02 | PXD058566 | Pride
Project description:Transriptional profiling of white adipose tissue extracted from obese mice. White adipose tissues were extrated from Oma1-deficient mouse and control after 20 weeks of diet-induced obesity. RNA were extracted and hybridated with Mouse Gene 1.0 ST from Affymetrix microarrays.
2012-01-01 | E-GEOD-27525 | biostudies-arrayexpress
Project description:Differential gene expression in CHCHD10 G58R mouse hearts treated with nontargeting or OMA1-targeting antisense oligomers (ASOs) provided by Ionis Pharmaceuticals (Carlsbad, CA) This experiment used the Clariom_S_Mouse Microarray from Affymetrix to analyze the effect of acute OMA1 KD on gene expression in CHCHD10 G58R mouse hearts.
2022-06-30 | GSE189396 | GEO
Project description:Differential gene expression in CHCHD10 mutants with OMA1 present or knocked out This experiment used the Clariom_S_Mouse Microarray from Affymetrix to analyze the effect of CHCHD10 mutations on gene expression, and the effect of congenital OMA1 KO on gene expression in these CHCHD10 mutants.
2022-06-30 | GSE189393 | GEO
Project description:Mitochondrial dysfunction causes devastating disorders, including mitochondrial myopathy. Here, we identified that diverse mitochondrial myopathy models elicit a protective mitochondrial integrated stress response (mt-ISR), mediated by OMA1-DELE1 signaling. The response was similar following disruptions in mtDNA maintenance, from knockout of Tfam, and mitochondrial protein unfolding, from disease-causing mutations in CHCHD10 (G58R and S59L). The preponderance of the response was directed at upregulating pathways for aminoacyl-tRNA biosynthesis, the intermediates for protein synthesis, and was similar in heart and skeletal muscle but more limited in brown adipose challenged with cold stress. Strikingly, models with early DELE1 mt-ISR activation failed to grow and survive to adulthood in the absence of Dele1, accounting for some but not all of OMA1’s protection. Notably, the DELE1 mt-ISR did not slow net protein synthesis in stressed striated muscle, but instead prevented loss of translation-associated proteostasis in muscle fibers. Together our findings identify that the DELE1 mt-ISR mediates a stereotyped response to diverse forms of mitochondrial stress and is particularly critical for maintaining growth and survival in early-onset mitochondrial myopathy. This experiment used the Clariom_S_Mouse Microarray from Affymetrix/Applied Biosystems to analyze the effect of knocking down OMA1 by ASO in CHCHD10 G58R mouse model of mitochondrial myopathy/cardiomyopathy.
2024-07-13 | GSE271792 | GEO
Project description:Mitochondrial proteases regulate the dynamic properties of the organelle morphology and ensure functional plasticity at the cellular level. The metalloprotease OMA1 mediates constitutive and stress-inducible processing of its substrates in mitochondria, but the number of functionally characterized substrates remains limited. Using multiproteomic and biochemical approaches, we show that the membrane-anchored inner membrane space (IMS) protein AIFM1 serves as a mitochondrial stress-responsive substrate of OMA1. We define that OMA1 cleaves AIFM1 in the IMS under stress conditions, which is a kinetically slower reaction than that of the conventional substrate, the dynamin-like GTPase OPA1. Membrane dislocation of the cleaved AIFM1 in mitochondria leads to reduced binding to subunits of the oxidative phosphorylation machinery. This leads to a decrease in the respiratory activity and ultimately impairs cell growth. Mechanistically, we show that AIFM1 broadly safeguards the mitochondrial proteome at steady state by participating in the protein import, in particular respiratory complex I subunits, via the Tim23 complex. These results reveal an unrecognized role of OMA1 for integrating mitochondrial stress sensing and cellular energetics by altering the topology of AIFM1.
2026-01-30 | GSE296062 | GEO
Project description:Mitochondrial dysfunction causes devastating disorders, including mitochondrial myopathy. Here, we identified that diverse mitochondrial myopathy models elicit a protective mitochondrial integrated stress response (mt-ISR), mediated by OMA1-DELE1 signaling. The response was similar following disruptions in mtDNA maintenance, from knockout of Tfam, and mitochondrial protein unfolding, from disease-causing mutations in CHCHD10 (G58R and S59L). The preponderance of the response was directed at upregulating pathways for aminoacyl-tRNA biosynthesis, the intermediates for protein synthesis, and was similar in heart and skeletal muscle but more limited in brown adipose challenged with cold stress. Strikingly, models with early DELE1 mt-ISR activation failed to grow and survive to adulthood in the absence of Dele1, accounting for some but not all of OMA1’s protection. Notably, the DELE1 mt-ISR did not slow net protein synthesis in stressed striated muscle, but instead prevented loss of translation-associated proteostasis in muscle fibers. Together our findings identify that the DELE1 mt-ISR mediates a stereotyped response to diverse forms of mitochondrial stress and is particularly critical for maintaining growth and survival in early-onset mitochondrial myopathy. This experiment used the Clariom_S_Mouse Microarray from Affymetrix/Applied Biosystems to analyze the effect of Dele1 KO and OMA1 KO under cold stress.
2024-07-31 | GSE273199 | GEO
Project description:To understand how OMA1 affects mitochondrial proteostasis and stress responses, we performed a proteomic survey of OMA1-deficient cells for proteolytic substrates. We demonstrate that OMA1 cleaves the mitochondrial chaperone DNAJC15 facilitating its degradation by the mitochondrial m-AAA protease. The loss of DNAJC15 alters protein import by TIM23 protein translocases in the IM and limits the accumulation of OXPHOS-related mitochondrial matrix and IM proteins. Non-imported mitochondrial preproteins accumulate at the endoplasmic reticulum (ER) and trigger an ATF6-related unfolded protein response. These results demonstrate that OMA1 allows to adapt mitochondrial protein biogenesis to stress and reveal an intricate network of cellular stress responses to proteostasis disturbances. In this dataset, we investigated the Neo-N terminal of proteins dependent on Oma1. In the original publication, only Oma1 and WT were utilized, while this dataset also contains MICS1 knockout and Oligomycin treatment.
2025-12-19 | PXD061134 | Pride
Project description: Not available
| S-EPMC11530700 | biostudies-literature