Dual role of Miro protein clusters in mitochondrial cristae organisation and ER-Mitochondria Contact Sites

Modi, S. and Lopez-Deomenech, G. and Halff, E. and Covill-Cooke, C. and Ivankovic, D. and Melandri, D. and Arancivia-Carcamo, L. and Burden, J. and Lowe, Alan and Kittler, J. (2019) Dual role of Miro protein clusters in mitochondrial cristae organisation and ER-Mitochondria Contact Sites. Nature Communications 10 (4399), ISSN 2041-1723.

Abstract

Mitochondrial Rho (Miro) GTPases localize to the outer mitochondrial membrane and are essential machinery for the regulated trafficking of mitochondria to defined subcellular locations. However, their sub-mitochondrial localization and relationship with other critical mitochondrial complexes remains poorly understood. Here, using super-resolution fluorescence microscopy, we report that Miro proteins form nanometer-sized clusters along the mitochondrial outer membrane in association with the Mitochondrial Contact Site and Cristae Organizing System (MICOS). Using knockout mouse embryonic fibroblasts (MEF) we show that Miro1 and Miro2 are required for normal mitochondrial cristae architecture and endoplasmic reticulum-mitochondria contacts sites (ERMCS). Further, we show that Miro couples MICOS to TRAK motor protein adaptors to ensure the concerted transport of the two mitochondrial membranes and the correct distribution of cristae on the mitochondrial membrane. The Miro nanoscale organization, association with MICOS complex and regulation of ERMCS reveal new levels of control of the Miro GTPases on mitochondrial functionality.

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