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Shared structural features of Miro binding control mitochondrial homeostasis

Covill-Cooke, Christian; Kwizera, Brian; López-Doménech, Guillermo; Thompson, Caleb OD; Cheung, Ngaam J; Cerezo, Ema; Peterka, Martin; ... Kornmann, Benoît; + view all (2024) Shared structural features of Miro binding control mitochondrial homeostasis. The EMBO Journal 10.1038/s44318-024-00028-1. (In press). Green open access

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Abstract

Miro proteins are universally conserved mitochondrial calcium-binding GTPases that regulate a multitude of mitochondrial processes, including transport, clearance, and lipid trafficking. The exact role of Miro in these functions is unclear but involves binding to a variety of client proteins. How this binding is operated at the molecular level and whether and how it is important for mitochondrial health, however, remains unknown. Here, we show that known Miro interactors—namely, CENPF, Trak, and MYO19—all use a similar short motif to bind the same structural element: a highly conserved hydrophobic pocket in the first calcium-binding domain of Miro. Using these Miro-binding motifs, we identified direct interactors de novo, including MTFR1/2/1L, the lipid transporters Mdm34 and VPS13D, and the ubiquitin E3-ligase Parkin. Given the shared binding mechanism of these functionally diverse clients and its conservation across eukaryotes, we propose that Miro is a universal mitochondrial adaptor coordinating mitochondrial health.

Type: Article
Title: Shared structural features of Miro binding control mitochondrial homeostasis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s44318-024-00028-1
Publisher version: http://dx.doi.org/10.1038/s44318-024-00028-1
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10186447
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