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Clueless-CLUH regulates mitochondrial fission by promoting recruitment of Drp1 to mitochondria7.01 MB
Published VersionCC BY V4.0, Open Access
Journal article
Clueless/CLUH regulates mitochondrial fission by promoting recruitment of Drp1 to mitochondria
Nature Communications, Vol.13(1), pp.1-19
2022
PMID: 35332133
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USC NewsAbstract
Mitochondrial fission is critically important for controlling mitochondrial morphology, function, quality and transport. Drp1 is the master regulator driving mitochondrial fission, but exactly how Drp1 is regulated remains unclear. Here, we identified Drosophila Clueless and its mammalian orthologue CLUH as key regulators of Drp1. As with loss of drp1, depletion of clueless or CLUH results in mitochondrial elongation, while as with drp1 overexpression, clueless or CLUH overexpression leads to mitochondrial fragmentation. Importantly, drp1 overexpression rescues adult lethality, tissue disintegration and mitochondrial defects of clueless null mutants in Drosophila. Mechanistically, Clueless and CLUH promote recruitment of Drp1 to mitochondria from the cytosol. This involves CLUH binding to mRNAs encoding Drp1 receptors MiD49 and Mff, and regulation of their translation. Our findings identify a crucial role of Clueless and CLUH in controlling mitochondrial fission through regulation of Drp1.
Details
- Title
- Clueless/CLUH regulates mitochondrial fission by promoting recruitment of Drp1 to mitochondria
- Authors
- Huan Yang (Author) - David Geffen School of Medicine at UCLACaroline Sibilla (Author) - University College LondonR Liu (Author) - California Institute of TechnologyJina Yun (Author) - David Geffen School of Medicine at UCLAB Hay (Author) - California Institute of TechnologyCraig Blackstone (Author) - Harvard Medical SchoolDavid C Chan (Author) - California Institute of TechnologyRobert Harvey (Author) - University of the Sunshine Coast, Queensland, School of Health and Behavioural Sciences - LegacyM Guo (Corresponding Author) - David Geffen School of Medicine at UCLA
- Publication details
- Nature Communications, Vol.13(1), pp.1-19
- Publisher
- Nature Publishing Group
- Date published
- 2022
- DOI
- 10.1038/s41467-022-29071-4
- ISSN
- 2041-1723
- PMID
- 35332133
- Copyright note
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Organisation Unit
- School of Health; University of the Sunshine Coast, Queensland; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99625440702621
- Output Type
- Journal article
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