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

Autor: Nicol Birsa, Viktoriya S Toncheva, Guillermo López-Doménech, Christian Covill-Cooke, James Drew, Josef T. Kittler
Rok vydání: 2020
Předmět:
Zdroj: EMBO Reports
EMBO Rep
ISSN: 1469-3178
1469-221X
DOI: 10.15252/embr.201949865
Popis: 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.
Miro1 and Miro2 localise to peroxisomes and negatively regulate peroxisomal fission rather than long‐range transport and distribution.
Databáze: OpenAIRE