ArticleThe EMBO journal2020
Mitochondrial Safeguard: a stress response that offsets extreme fusion and protects respiratory function via flickering-induced Oma1 activation.
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Mitochondria‑endoplasmic reticulum contact site nexus: Molecular integration, disease pathogenesis and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Stress-induced OMA1-mediated cleavage of AIFM1 suppresses cell growth by controlling mitochondrial OXPHOS activity.The EMBO journal · 2026Article
- Proteolytic control of mitochondrial protein translocases.Protein science : a publication of the Protein Society · 2026Review
- Mitochondrial dynamics and cancer: mechanisms and targeted therapy.Cell biology and toxicology · 2026Review
- Palmitic acid induces UCP1-independent mitochondrial depolarization specifically in brown adipose tissue.The Journal of biological chemistry · 2026Article
- A unified mechanism for mitochondrial damage sensing in PINK1-Parkin-mediated mitophagy.The EMBO journal · 2026Article
- Context-dependent inhibitory roles of RhoA in 3D invasive cell migration within the extracellular matrix.Cell reports · 2025Article
- Targeting mitochondrial structure and dynamics for therapeutic intervention in cancer.PLoS biology · 2025Article
- Charcot-Marie-Tooth type 2A variants of mitofusin 2 sensitize cells to apoptotic cell death.Journal of cell science · 2025Article
- 0.01% atropine combined with carteolol hydrochloride can inhibit the scleral remodeling in guinea pigs with form-deprivation myopia.Scientific reports · 2025Article
- A Molecular Chemical Perspective: Mitochondrial Dynamics Is Not a Bystander of Cartilage Diseases.ACS pharmacology & translational science · 2025Review
- Copper Chelation Induces Morphology Change in Mitochondria of Triple-Negative Breast Cancer.JACS Au · 2025Article
- Macrophage-derived mitochondria-rich extracellular vesicles aggravate bone loss in periodontitis by disrupting the mitochondrial dynamics of BMSCs.Journal of nanobiotechnology · 2025Article
- Article
- Mitofusin 2 displays fusion-independent roles in proteostasis surveillance.Nature communications · 2025Article
- Molecular mechanisms of mitochondrial dynamics.Nature reviews. Molecular cell biology · 2025Review
- DELE1 maintains muscle proteostasis to promote growth and survival in mitochondrial myopathy.The EMBO journal · 2024Article
- Slc25a3-dependent copper transport controls flickering-induced Opa1 processing for mitochondrial safeguard.Developmental cell · 2024Article
- Systemic phospho-defective and phospho-mimetic Drp1 mice exhibit normal growth and development with altered anxiety-like behavior.iScience · 2024Article
- OMA1-Mediated Mitochondrial Dynamics Balance Organellar Homeostasis Upstream of Cellular Stress Responses.International journal of molecular sciences · 2024Review
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8 authors at 2 institutions in 2 countries.
Funding
Abstract
The connectivity of mitochondria is regulated by a balance between fusion and division. Many human diseases are associated with excessive mitochondrial connectivity due to impaired Drp1, a dynamin-related GTPase that mediates division. Here, we report a mitochondrial stress response, named mitochondrial safeguard, that adjusts the balance of fusion and division in response to increased mitochondrial connectivity. In cells lacking Drp1, mitochondria undergo hyperfusion. However, hyperfusion does not completely connect mitochondria because Opa1 and mitofusin 1, two other dynamin-related GTPases that mediate fusion, become proteolytically inactivated. Pharmacological and genetic experiments show that the activity of Oma1, a metalloprotease that cleaves Opa1, is regulated by short pulses of the membrane depolarization without affecting the overall membrane potential in Drp1-knockout cells. Re-activation of Opa1 and Mitofusin 1 in Drp1-knockout cells further connects mitochondria beyond hyperfusion, termed extreme fusion, leading to bioenergetic deficits. These findings reveal an unforeseen safeguard mechanism that prevents extreme fusion of mitochondria, thereby maintaining mitochondrial function when the balance is shifted to excessive connectivity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.