ArticleThe Journal of cell biology2021
Parkin-independent mitophagy via Drp1-mediated outer membrane severing and inner membrane ubiquitination.
Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Roles of mitochondrial fusion and fission in breast cancer progression: a systematic review.World journal of surgical oncology · 2022Pooled it
- Review
- The pivotal role of mitochondria in the pathogenesis and treatment of liver failure: a comprehensive review.Molecular and cellular biochemistry · 2026Review
- The multifaceted functions of selective autophagy in cancer: molecular basis, consequences, and clinical prospects.Molecular cancer · 2026Review
- The Role of Ubiquitination and Deubiquitination in the Pathogenesis of Acute Kidney Injury: Progress in Research.Biomedicines · 2025Review
- Therapeutic potential of melatonin-induced mitophagy in the pathogenesis of Alzheimer's disease.Inflammopharmacology · 2025Review
- The Mitochondrial Foundations of Parkinson's Disease: Therapeutic Implications.Aging and disease · 2025Review
- Acute diacylglycerol production activates critical membrane-shaping proteins leading to mitochondrial tubulation and fission.Nature communications · 2025Article
- Functionally conserved inner mitochondrial membrane proteins CCDC51 and Mdm33 demarcate a subset of fission events.The Journal of cell biology · 2025Article
- Outer mitochondrial membrane E3 Ub ligase MARCH5 controls de novo peroxisome biogenesis.Developmental cell · 2025Article
- Mitochondrial fission process 1 protein: a comprehensive review of its core roles in mitochondrial dynamics, disease, and therapeutic targets.Frontiers in cell and developmental biology · 2025Review
- Mitochondrial DNA Instability Supersedes Parkin Mutations in Driving Mitochondrial Proteomic Alterations and Functional Deficits in Polg Mutator Mice.International journal of molecular sciences · 2024Article
- Burkholderia pseudomallei BipD modulates host mitophagy to evade killing.Nature communications · 2024Article
- Serotonin regulation of mitochondria in kidney diseases.Pharmacological research · 2024Review
- Human CCDC51 and yeast Mdm33 are functionally conserved mitochondrial inner membrane proteins that demarcate a subset of organelle fission events.bioRxiv : the preprint server for biology · 2024Article
- Exposure of the inner mitochondrial membrane triggers apoptotic mitophagy.Cell death and differentiation · 2024Article
- Insulin signalling regulates Pink1 mRNA localization via modulation of AMPK activity to support PINK1 function in neurons.Nature metabolism · 2024Article
- Mitochondrial abnormalities as a target of intervention in acute myeloid leukemia.Frontiers in oncology · 2024Review
- The role of SIRT3 in homeostasis and cellular health.Frontiers in cellular neuroscience · 2024Review
- Mitophagy in human health, ageing and disease.Nature metabolism · 2023Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Here, we report that acute reduction in mitochondrial translation fidelity (MTF) causes ubiquitination of the inner mitochondrial membrane (IMM) proteins, including TRAP1 and CPOX, which occurs selectively in mitochondria with a severed outer mitochondrial membrane (OMM). Ubiquitinated IMM recruits the autophagy machinery. Inhibiting autophagy leads to increased accumulation of mitochondria with severed OMM and ubiquitinated IMM. This process occurs downstream of the accumulation of cytochrome c/CPOX in a subset of mitochondria heterogeneously distributed throughout the cell ("mosaic distribution"). Formation of mosaic mitochondria, OMM severing, and IMM ubiquitination require active mitochondrial translation and mitochondrial fission, but not the proapoptotic proteins Bax and Bak. In contrast, in Parkin-overexpressing cells, MTF reduction does not lead to the severing of the OMM or IMM ubiquitination, but it does induce Drp1-independent ubiquitination of the OMM. Furthermore, high-cytochrome c/CPOX mitochondria are preferentially targeted by Parkin, indicating that in the context of reduced MTF, they are mitophagy intermediates regardless of Parkin expression. In sum, Parkin-deficient cells adapt to mitochondrial proteotoxicity through a Drp1-mediated mechanism that involves the severing of the OMM and autophagy targeting ubiquitinated IMM proteins.
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Registered trials
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.