Mitochondria are highly dynamic organelles undergoing coordinated cycles of fission and fusion, referred as ‘mitochondrial dynamics’, in order to maintain their shape, distribution and size. Their transient and rapid morphological adaptations are crucial for many cellular processes such as cell cycle, immunity, apoptosis and mitochondrial quality control. Mutations in the core machinery components and defects in mitochondrial dynamics have been associated with numerous human diseases. These dynamic transitions are mainly ensured by large GTPases belonging to the Dynamin family. Mitochondrial fission is a multi-step process allowing the division of one mitochondrion in two daughter mitochondria. It is regulated by the recruitment of the GTPase Dynamin-related protein 1 (Drp1) by adaptors at actin- and endoplasmic reticulum-mediated mitochondrial constriction sites. Drp1 oligomerization followed by mitochondrial constriction leads to the recruitment of Dynamin 2 to terminate membrane scission. Inner mitochondrial membrane constriction has been proposed to be an independent process regulated by calcium influx. Mitochondrial fusion is driven by a two-step process with the outer mitochondrial membrane fusion mediated by mitofusins 1 and 2 followed by inner membrane fusion, mediated by optic atrophy 1. In addition to the role of membrane lipid composition, several members of the machinery can undergo post-translational modifications modulating these processes. Understanding the molecular mechanisms controlling mitochondrial dynamics is crucial to decipher how mitochondrial shape meets the function and to increase the knowledge on the molecular basis of diseases associated with morphology defects. This article will describe an overview of the molecular mechanisms that govern mitochondrial fission and fusion in mammals.

Peroxisomes function together with mitochondria in a number of essential biochemical pathways, from bile acid synthesis to fatty acid oxidation. Peroxisomes grow and divide from pre-existing organelles, but can also emerge de novo in the cell. The physiological regulation of de novo peroxisome biogenesis remains unclear, and it is thought that peroxisomes emerge from the endoplasmic reticulum in both mammalian and yeast cells. However, in contrast to the yeast system, a number of integral peroxisomal membrane proteins are imported into mitochondria in mammalian cells in the absence of peroxisomes, including Pex3, Pex12, Pex13, Pex14, Pex26, PMP34 and ALDP. Overall, the mitochondrial localization of peroxisomal membrane proteins in mammalian cells has largely been considered a mis-targeting artefact in which de novo biogenesis occurs exclusively from endoplasmic reticulum-targeted peroxins. Here, in following the generation of new peroxisomes within human patient fibroblasts lacking peroxisomes, we show that the essential import receptors Pex3 and Pex14 target mitochondria, where they are selectively released into vesicular pre-peroxisomal structures. Maturation of pre-peroxisomes containing Pex3 and Pex14 requires fusion with endoplasmic reticulum-derived vesicles carrying Pex16, thereby providing full import competence. These findings demonstrate the hybrid nature of newly born peroxisomes, expanding their functional links to mitochondria.