VPS13D bridges the ER to mitochondria and peroxisomes via Miro
| Autor: | Pietro De Camilli, Michael G. Hanna, Hongying Shen, Andrés Guillén-Samander, Ni Tang, Marianna Leonzino |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | VPS13D mutations result in severe mitochondrial defects. Guillén-Samander et al. show that VPS13D binds VAP in the ER and interacts with Miro on mitochondria and peroxisomes, where it could provide a bridge for lipid transport between these organelles. Mitochondria, which are excluded from the secretory pathway, depend on lipid transport proteins for their lipid supply from the ER, where most lipids are synthesized. In yeast, the outer mitochondrial membrane GTPase Gem1 is an accessory factor of ERMES, an ER–mitochondria tethering complex that contains lipid transport domains and that functions, partially redundantly with Vps13, in lipid transfer between the two organelles. In metazoa, where VPS13, but not ERMES, is present, the Gem1 orthologue Miro was linked to mitochondrial dynamics but not to lipid transport. Here we show that Miro, including its peroxisome-enriched splice variant, recruits the lipid transport protein VPS13D, which in turn binds the ER in a VAP-dependent way and thus could provide a lipid conduit between the ER and mitochondria. These findings reveal a so far missing link between function(s) of Gem1/Miro in yeast and higher eukaryotes, where Miro is a Parkin substrate, with potential implications for Parkinson’s disease pathogenesis. |
| Databáze: | OpenAIRE |
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