期刊
EMBO JOURNAL
卷 37, 期 3, 页码 321-336出版社
WILEY
DOI: 10.15252/embj.201696380
关键词
micropattern; myosin XIX; Rhot1; Rhot2; mitofusin
资金
- ERC starting grant [282430]
- Lister Institute for Preventive Medicine
- Medical Research Council
- MRC LMCB PhD programme at UCL (MRC studentship) [1368635]
- MRC CASE Award
- Brain Research Trust PhD Scholarship on the UCL Clinical Neuroscience Program
- Marie Sklodowska-Curie grant [661733]
- European Research Council (ERC) [282430] Funding Source: European Research Council (ERC)
- Medical Research Council [1368635] Funding Source: researchfish
- Marie Curie Actions (MSCA) [661733] Funding Source: Marie Curie Actions (MSCA)
In the current model of mitochondrial trafficking, Miro1 and Miro2 Rho-GTPases regulate mitochondrial transport along microtubules by linking mitochondria to kinesin and dynein motors. By generating Miro1/2 double-knockout mouse embryos and single-and double-knockout embryonic fibroblasts, we demonstrate the essential and non-redundant roles of Miro proteins for embryonic development and subcellular mitochondrial distribution. Unexpectedly, the TRAK1 and TRAK2 motor protein adaptors can still localise to the outer mitochondrial membrane to drive anterograde mitochondrial motility in Miro1/2 double-knockout cells. In contrast, we show that TRAK2-mediated retrograde mitochondrial transport is Miro1-dependent. Interestingly, we find that Miro is critical for recruiting and stabilising the mitochondrial myosin Myo19 on the mitochondria for coupling mitochondria to the actin cytoskeleton. Moreover, Miro depletion during PINK1/Parkin-dependent mitophagy can also drive a loss of mitochondrial Myo19 upon mitochondrial damage. Finally, aberrant positioning of mitochondria in Miro1/2 double-knockout cells leads to disruption of correct mitochondrial segregation during mitosis. Thus, Miro proteins can fine-tune actin-and tubulin-dependent mitochondrial motility and positioning, to regulate key cellular functions such as cell proliferation.
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