Ubiquitin Ligase MARCH5 Regulates the Formation of Mitochondria Derived Pre-peroxisomes

Abstract

ABSTRACTPeroxisome biogenesis involves two pathways: growth and division from pre-existing mature peroxisomes andde novobiogenesis from the endoplasmic reticulum, with a contribution from mitochondria, particularly in peroxisome deficient cells. However, the key components that regulate peroxisomede novobiogenesis are largely unknown. Dual organelle localized ubiquitin ligase MARCH5 functions on peroxisomes to regulate pexophagy. Here, we show that mitochondria localized MARCH5 is essential for the formation of vesicles in thede novobiogenesis of peroxisomes from mitochondria. Loss of MARCH5 specifically impedes the budding of PEX3-containing vesicles from mitochondria, thereby blocking the formation of pre-peroxisomes. Overall, our study highlights a novel function of MARCH5 for mitochondria derived pre-peroxisomes, emphasizing MARCH5 as one key regulator to maintain peroxisome homeostasis.