Peroxisomes are essential for a number of cellular functions, including reactive oxygen species metabolism, fatty acid b-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.

Peroxisomes are organelles that perform a wide range of essential metabolic processes. To ensure that peroxisomes are optimally positioned in the cell, they must be transported by both long- and short-range trafficking events in response to cellular needs. Here, we review our current understanding of the mechanisms by which the cytoskeleton and organelle contact sites alter peroxisomal distribution. Though the focus of the review is peroxisomal transport in mammalian cells, findings from flies and fungi are used for comparison and to inform the gaps in our understanding. Attention is given to the apparent overlap in regulatory mechanisms for mitochondrial and peroxisomal trafficking, along with the recently discovered role of the mitochondrial Rho-GTPases, Miro, in peroxisomal dynamics. Moreover, we outline and discuss the known pathological and pharmacological conditions that perturb peroxisomal positioning. We conclude by highlighting several gaps in our current knowledge and suggest future directions that require attention.