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Peroxisomal fission is modulated by the mitochondrial Rho-GTPases, Miro1 and Miro2

Covill-Cooke, C; Toncheva, VS; Drew, J; Birsa, N; López-Doménech, G; Kittler, JT; (2020) Peroxisomal fission is modulated by the mitochondrial Rho-GTPases, Miro1 and Miro2. EMBO Reports , Article e49865. 10.15252/embr.201949865. Green open access

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Abstract

Peroxisomes are essential for a number of cellular functions, including reactive oxygen species metabolism, fatty acid β-oxidation and lipid synthesis. To ensure optimal functionality, peroxisomal size, shape and number must be dynamically maintained; however, many aspects of how this is regulated remain poorly characterised. Here, we show that the localisation of Miro1 and Miro2-outer mitochondrial membrane proteins essential for mitochondrial trafficking-to peroxisomes is not required for basal peroxisomal distribution and long-range trafficking, but rather for the maintenance of peroxisomal size and morphology through peroxisomal fission. Mechanistically, this is achieved by Miro negatively regulating Drp1-dependent fission, a function that is shared with the mitochondria. We further find that the peroxisomal localisation of Miro is regulated by its first GTPase domain and is mediated by an interaction through its transmembrane domain with the peroxisomal-membrane protein chaperone, Pex19. Our work highlights a shared regulatory role of Miro in maintaining the morphology of both peroxisomes and mitochondria, supporting a crosstalk between peroxisomal and mitochondrial biology.

Type: Article
Title: Peroxisomal fission is modulated by the mitochondrial Rho-GTPases, Miro1 and Miro2
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/embr.201949865
Publisher version: https://doi.org/10.15252/embr.201949865
Language: English
Additional information: © 2020 The Authors. Published under the terms of the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Keywords: Fis1, Rhot1, Rhot2, oscillatory, tail-anchored
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 Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
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/10089066
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