ArticleThe Journal of cell biology2022
Mid51/Fis1 mitochondrial oligomerization complex drives lysosomal untethering and network dynamics.
Article in The Journal of cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Mitochondrial Fis1 tunes Rab7A activity via TBC1D15 modulating STING degradation.Cell reports · 2026Article
- Review
- Spatial architecture of immunometabolism: Mitochondrial‑organelle interfaces in immune signaling (Review).International journal of molecular medicine · 2026Review
- Frontotemporal dementia associated CHCHD10Cell death & disease · 2026Article
- Smart Nanoparticles Disrupting Energy Supply through Triple Mechanisms to Kill Tumors via Dual Disruption of Mitochondria and Lysosomes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondrial dysfunction in mesenchymal stem cells impairs osteogenesis in radiation-induced bone injury via CaCell death & disease · 2025Article
- Fis1 regulates mitochondrial morphology, bioenergetics and removal of mitochondrial DNA damage in irradiated glioblastoma cells.Journal of cell science · 2025Article
- Mitochondrial fission - changing perspectives for future progress.Journal of cell science · 2025Review
- Syntaxin 17 Translocation Mediated Mitophagy Switching Drives Hyperglycemia-Induced Vascular Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- VPS13C regulates phospho-Rab10-mediated lysosomal function in human dopaminergic neurons.The Journal of cell biology · 2024Article
- Mitochondrial dysfunction induced by HIF-1α under hypoxia contributes to the development of gastric mucosal lesions.Clinical and translational medicine · 2024Article
- Multiple roles of mitochondrial autophagy receptor FUNDC1 in mitochondrial events and kidney disease.Frontiers in cell and developmental biology · 2024Review
- Novel strategies targeting mitochondria-lysosome contact sites for the treatment of neurological diseases.Frontiers in molecular neuroscience · 2024Review
- The mystery of phospho-Drp1 with four adaptors in cell cycle: when mitochondrial fission couples to cell fate decisions.Cell cycle (Georgetown, Tex.) · 2023Article
- Misregulation of mitochondria-lysosome contact dynamics in Charcot-Marie-Tooth Type 2B disease Rab7 mutant sensory peripheral neurons.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Multifaceted functions of Drp1 in hypoxia/ischemia-induced mitochondrial quality imbalance: from regulatory mechanism to targeted therapeutic strategy.Military Medical Research · 2023Review
- Parkin regulates amino acid homeostasis at mitochondria-lysosome (M/L) contact sites in Parkinson's disease.Science advances · 2023Article
- Hypoxia-reprogramed megamitochondrion contacts and engulfs lysosome to mediate mitochondrial self-digestion.Nature communications · 2023Article
- Selective inhibitors targeting Fis1/Mid51 protein-protein interactions protect against hypoxia-induced damage in cardiomyocytes.Frontiers in pharmacology · 2023Article
- Super-Resolution Microscopy to Study Interorganelle Contact Sites.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Lysosomes are highly dynamic organelles implicated in multiple diseases. Using live super-resolution microscopy, we found that lysosomal tethering events rarely undergo lysosomal fusion, but rather untether over time to reorganize the lysosomal network. Inter-lysosomal untethering events are driven by a mitochondrial Mid51/Fis1 complex that undergoes coupled oligomerization on the outer mitochondrial membrane. Importantly, Fis1 oligomerization mediates TBC1D15 (Rab7-GAP) mitochondrial recruitment to drive inter-lysosomal untethering via Rab7 GTP hydrolysis. Moreover, inhibiting Fis1 oligomerization by either mutant Fis1 or a Mid51 oligomerization mutant potentially associated with Parkinson's disease prevents lysosomal untethering events, resulting in misregulated lysosomal network dynamics. In contrast, dominant optic atrophy-linked mutant Mid51, which does not inhibit Mid51/Fis1 coupled oligomerization, does not disrupt downstream lysosomal dynamics. As Fis1 conversely also regulates Mid51 oligomerization, our work further highlights an oligomeric Mid51/Fis1 mitochondrial complex that mechanistically couples together both Drp1 and Rab7 GTP hydrolysis machinery at mitochondria-lysosome contact sites. These findings have significant implications for organelle networks in cellular homeostasis and human disease.
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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.