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

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 demon...

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Autores principales: López‐Doménech, Guillermo, Covill‐Cooke, Christian, Ivankovic, Davor, Halff, Els F, Sheehan, David F, Norkett, Rosalind, Birsa, Nicol, Kittler, Josef T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793800/
https://www.ncbi.nlm.nih.gov/pubmed/29311115
http://dx.doi.org/10.15252/embj.201696380
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author López‐Doménech, Guillermo
Covill‐Cooke, Christian
Ivankovic, Davor
Halff, Els F
Sheehan, David F
Norkett, Rosalind
Birsa, Nicol
Kittler, Josef T
author_facet López‐Doménech, Guillermo
Covill‐Cooke, Christian
Ivankovic, Davor
Halff, Els F
Sheehan, David F
Norkett, Rosalind
Birsa, Nicol
Kittler, Josef T
author_sort López‐Doménech, Guillermo
collection PubMed
description 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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spelling pubmed-57938002018-02-12 Miro proteins coordinate microtubule‐ and actin‐dependent mitochondrial transport and distribution López‐Doménech, Guillermo Covill‐Cooke, Christian Ivankovic, Davor Halff, Els F Sheehan, David F Norkett, Rosalind Birsa, Nicol Kittler, Josef T EMBO J Articles 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. John Wiley and Sons Inc. 2018-01-08 2018-02-01 /pmc/articles/PMC5793800/ /pubmed/29311115 http://dx.doi.org/10.15252/embj.201696380 Text en © 2018 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
López‐Doménech, Guillermo
Covill‐Cooke, Christian
Ivankovic, Davor
Halff, Els F
Sheehan, David F
Norkett, Rosalind
Birsa, Nicol
Kittler, Josef T
Miro proteins coordinate microtubule‐ and actin‐dependent mitochondrial transport and distribution
title Miro proteins coordinate microtubule‐ and actin‐dependent mitochondrial transport and distribution
title_full Miro proteins coordinate microtubule‐ and actin‐dependent mitochondrial transport and distribution
title_fullStr Miro proteins coordinate microtubule‐ and actin‐dependent mitochondrial transport and distribution
title_full_unstemmed Miro proteins coordinate microtubule‐ and actin‐dependent mitochondrial transport and distribution
title_short Miro proteins coordinate microtubule‐ and actin‐dependent mitochondrial transport and distribution
title_sort miro proteins coordinate microtubule‐ and actin‐dependent mitochondrial transport and distribution
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793800/
https://www.ncbi.nlm.nih.gov/pubmed/29311115
http://dx.doi.org/10.15252/embj.201696380
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