2020
EMBO reports

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

Authors:

Covill‐Cooke, C., Toncheva, V. S., Drew, J., Birsa, N., López‐Doménech, G., & Kittler, J. T.

Keywords:

Fis1, oscillatory, Rhot1, Rhot2, tail-anchored, mitochondria

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.