Miro proteins coordinate microtubule- and actin-dependent mitochondrial transport and distribution

EMBO J. 2018 Feb 1;37(3):321-336. doi: 10.15252/embj.201696380. Epub 2018 Jan 8.


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.

Keywords: Rhot1; Rhot2; micropattern; mitofusin; myosin XIX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adaptor Proteins, Vesicular Transport
  • Animals
  • Biological Transport
  • Carrier Proteins / metabolism
  • Cell Line, Transformed
  • Cell Proliferation / genetics
  • Dyneins / metabolism*
  • Embryonic Development / genetics
  • Kinesins / metabolism*
  • Mice
  • Mice, Knockout
  • Microtubules / metabolism
  • Mitochondria / metabolism*
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Proteins / genetics*
  • Myosins / metabolism*
  • Nerve Tissue Proteins / metabolism
  • Protein Kinases / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • rho GTP-Binding Proteins / genetics*


  • Actins
  • Adaptor Proteins, Vesicular Transport
  • Carrier Proteins
  • Miro-1 protein, mouse
  • Mitochondrial Proteins
  • Myo19 protein, mouse
  • Nerve Tissue Proteins
  • TRAK2 protein, mouse
  • Trak1 protein, mouse
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • PTEN-induced putative kinase
  • Rhot2 protein, mouse
  • Myosins
  • Dyneins
  • Kinesins
  • rho GTP-Binding Proteins