期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-12382-4
关键词
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资金
- ERC [282430]
- Lister Institute for Preventive Medicine prize
- Medical Research Council [MR/K015826/1]
- EMBO Long-Term Fellowship
- Marie Sklodowska-Curie International Incoming Fellowship [630033, 913033]
- European Union [661733]
- Institute of Neurology Clinical Neuroscience PhD
- MRC LMCB PhD program
- [MC_U12266B]
- Marie Curie Actions (MSCA) [661733] Funding Source: Marie Curie Actions (MSCA)
- European Research Council (ERC) [282430] Funding Source: European Research Council (ERC)
- MRC [MR/K015826/1] Funding Source: UKRI
Mitochondrial Rho (Miro) GTPases localize to the outer mitochondrial membrane and are essential machinery for the regulated trafficking of mitochondria to defined subcellular locations. However, their sub-mitochondrial localization and relationship with other critical mitochondrial complexes remains poorly understood. Here, using super-resolution fluorescence microscopy, we report that Miro proteins form nanometer-sized clusters along the mitochondrial outer membrane in association with the Mitochondrial Contact Site and Cristae Organizing System (MICOS). Using knockout mouse embryonic fibroblasts we show that Miro1 and Miro2 are required for normal mitochondrial cristae architecture and Endoplasmic Reticulum-Mitochondria Contacts Sites (ERMCS). Further, we show that Miro couples MICOS to TRAK motor protein adaptors to ensure the concerted transport of the two mitochondrial membranes and the correct distribution of cristae on the mitochondrial membrane. The Miro nanoscale organization, association with MICOS complex and regulation of ERMCS reveal new levels of control of the Miro GTPases on mitochondrial functionality.
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