TY - JOUR T1 - Dual role of Miro protein clusters in mitochondrial cristae organisation and ER-Mitochondria Contact Sites JF - bioRxiv DO - 10.1101/639948 SP - 639948 AU - Souvik Modi AU - Guillermo López-Doménech AU - Elise F. Halff AU - Christian Covill-Cooke AU - Davor Ivankovic AU - Daniela Melandri AU - Lorena Arancibia-Cárcamo AU - Jemima J. Burden AU - Alan R. Lowe AU - Josef T. Kittler Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/05/20/639948.abstract N2 - 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. ER -