ArticleProceedings of the National Academy of Sciences of the United States of America2024
Tom20 gates PINK1 activity and mediates its tethering of the TOM and TIM23 translocases upon mitochondrial stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- The molecular mechanisms of mitochondrial dynamics and mitophagy and their complex association with cancer drug resistance.Journal of translational medicine · 2025Pooled it
- Regulation of cellular proteostasis via mitochondrial protein import.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Transmembrane domain switching controls PINK1 import and fate in mitochondria.The EMBO journal · 2026Article
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Quality control of protein import into mammalian mitochondria.Protein science : a publication of the Protein Society · 2026Review
- A dynamic gateway: Uncovering the expanded human TOM complex interactome and its regulatory complexity.Science advances · 2026Article
- Phosphorylated ubiquitin is a secondary messenger and an epigenetic mark mediating mitochondria to nucleus signaling.bioRxiv : the preprint server for biology · 2026Article
- Two Routes for Removing Unhealthy Mitochondria: Degradation and Secretion.Circulation research · 2026Review
- HomozygousTranslational andrology and urology · 2026Article
- Function and regulation of the mitochondrial stress response.Nature structural & molecular biology · 2026Review
- The endoplasmic reticulum in mitochondrial protein targeting: A neuronal perspective on organelle crosstalk.Protein science : a publication of the Protein Society · 2026Review
- Isoflurane aggravates pre-existing proteotoxicity in adult nematodes by suppressing mitochondrial fitness.Scientific reports · 2026Article
- Host miRNA orchestration of mitophagy pathways during bacterial infection: current advances and future directions.Frontiers in microbiology · 2026Review
- Rethinking PINK1/Parkin-mediated mitophagy in Parkinson's disease: functional continuity and activation-clearance uncoupling.Frontiers in aging neuroscience · 2026Review
- Mastering cardiomyocyte mitophagy: molecular governance, pathological derailment and therapeutics.PeerJ · 2026Review
- A unified mechanism for mitochondrial damage sensing in PINK1-Parkin-mediated mitophagy.The EMBO journal · 2026Article
- Relevance and application of sirtuin 3-activated mitophagy in gastric cancer treatment.World journal of clinical oncology · 2025Review
- Ubiquitin-Specific Protease 20 Promotes CCCP-Induced Mitophagy Through Deubiquitination and Stabilization of Serine/Threonine Protein Kinase PINK1.Journal of molecular neuroscience : MN · 2025Article
- Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in PTEN-induced putative kinase 1 (PINK1) cause autosomal recessive early-onset Parkinson's disease (PD). PINK1 is a Ser/Thr kinase that regulates mitochondrial quality control by triggering mitophagy mediated by the ubiquitin (Ub) ligase Parkin. Upon mitochondrial damage, PINK1 accumulates on the outer mitochondrial membrane forming a high-molecular-weight complex with the translocase of the outer membrane (TOM). PINK1 then phosphorylates Ub, which enables recruitment and activation of Parkin followed by autophagic clearance of the damaged mitochondrion. Thus, Parkin-dependent mitophagy hinges on the stable accumulation of PINK1 on the TOM complex. Yet, the mechanism linking mitochondrial stressors to PINK1 accumulation and whether the translocases of the inner membrane (TIMs) are also involved remain unclear. Herein, we demonstrate that mitochondrial stress induces the formation of a PINK1-TOM-TIM23 supercomplex in human cultured cell lines, dopamine neurons, and midbrain organoids. Moreover, we show that PINK1 is required to stably tether the TOM to TIM23 complexes in response to stress such that the supercomplex fails to accumulate in cells lacking PINK1. This tethering is dependent on an interaction between the PINK1 N-terminal-C-terminal extension module and the cytosolic domain of the Tom20 subunit of the TOM complex, the disruption of which, by either designer or PD-associated PINK1 mutations, inhibits downstream mitophagy. Together, the findings provide key insight into how PINK1 interfaces with the mitochondrial import machinery, with important implications for the mechanisms of mitochondrial quality control and PD pathogenesis.
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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.