ArticleProtein & cell2018
Hypertonia-linked protein Trak1 functions with mitofusins to promote mitochondrial tethering and fusion.
Article in Protein & cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Article
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- Osteocyte mitochondria inhibit tumor development via STING-dependent antitumor immunity.Science advances · 2024Article
- Recurrent TRAK1::RAF1 Fusions in pediatric low-grade gliomas.Brain pathology (Zurich, Switzerland) · 2023Article
- Albumosomes formed by cytoplasmic pre-folding albumin maintain mitochondrial homeostasis and inhibit nonalcoholic fatty liver disease.Signal transduction and targeted therapy · 2023Article
- Spatial and temporal dynamics of ATP synthase from mitochondria toward the cell surface.Communications biology · 2023Article
- Genomics of Secondarily Temperate Adaptation in the Only Non-Antarctic Icefish.Molecular biology and evolution · 2023Article
- Miro GTPase domains regulate the assembly of the mitochondrial motor-adaptor complex.Life science alliance · 2023Article
- Disruption of mitochondrial quality control genes promotes caspase-resistant cell survival following apoptotic stimuli.The Journal of biological chemistry · 2022Article
- Article
- Miro proteins and their role in mitochondrial transfer in cancer and beyond.Frontiers in cell and developmental biology · 2022Review
- Mitochondrial dynamics, positioning and function mediated by cytoskeletal interactions.Cellular and molecular life sciences : CMLS · 2021Review
- TRAK1-Mediated Abnormality of Mitochondrial Fission Increases Seizure Susceptibility in Temporal Lobe Epilepsy.Molecular neurobiology · 2021Article
- Regulation of peroxisomal trafficking and distribution.Cellular and molecular life sciences : CMLS · 2021Review
- Mitochondrial dynamics: Shaping and remodeling an organelle network.Current opinion in cell biology · 2021Review
- Mitochondrial Quality Control Strategies: Potential Therapeutic Targets for Neurodegenerative Diseases?Frontiers in neuroscience · 2021Review
- Cdk5-mediated Drp1 phosphorylation drives mitochondrial defects and neuronal apoptosis in radiation-induced optic neuropathy.Cell death & disease · 2020Article
- Miro: A molecular switch at the center of mitochondrial regulation.Protein science : a publication of the Protein Society · 2020Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Hypertonia is a neurological dysfunction associated with a number of central nervous system disorders, including cerebral palsy, Parkinson's disease, dystonia, and epilepsy. Genetic studies have identified a homozygous truncation mutation in Trak1 that causes hypertonia in mice. Moreover, elevated Trak1 protein expression is associated with several types of cancers and variants in Trak1 are linked to childhood absence epilepsy in humans. Despite the importance of Trak1 in health and disease, the mechanisms of Trak1 action remain unclear and the pathogenic effects of Trak1 mutation are unknown. Here we report that Trak1 has a crucial function in regulation of mitochondrial fusion. Depletion of Trak1 inhibits mitochondrial fusion, resulting in mitochondrial fragmentation, whereas overexpression of Trak1 elongates and enlarges mitochondria. Our analyses revealed that Trak1 interacts and colocalizes with mitofusins on the outer mitochondrial membrane and functions with mitofusins to promote mitochondrial tethering and fusion. Furthermore, Trak1 is required for stress-induced mitochondrial hyperfusion and pro-survival response. We found that hypertonia-associated mutation impairs Trak1 mitochondrial localization and its ability to facilitate mitochondrial tethering and fusion. Our findings uncover a novel function of Trak1 as a regulator of mitochondrial fusion and provide evidence linking dysregulated mitochondrial dynamics to hypertonia pathogenesis.
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