Mitochondria are multifunctional organelles that not only produce energy for the cell, but are also important for cell signalling, apoptosis and many biosynthetic pathways. In most cell types, they fo Show more
Mitochondria are multifunctional organelles that not only produce energy for the cell, but are also important for cell signalling, apoptosis and many biosynthetic pathways. In most cell types, they form highly dynamic networks that are constantly remodelled through fission and fusion events, repositioned by motor-dependent transport and degraded when they become dysfunctional. Motor proteins and their tracks are key regulators of mitochondrial homeostasis, and in this Review, we discuss the diverse functions of the three classes of motor proteins associated with mitochondria - the actin-based myosins, as well as the microtubule-based kinesins and dynein. In addition, Miro and TRAK proteins act as adaptors that link kinesin-1 and dynein, as well as myosin of class XIX (MYO19), to mitochondria and coordinate microtubule- and actin-based motor activities. Here, we highlight the roles of motor proteins and motor-linked track dynamics in the transporting and docking of mitochondria, and emphasize their adaptations in specialized cells. Finally, we discuss how motor-cargo complexes mediate changes in mitochondrial morphology through fission and fusion, and how they modulate the turnover of damaged organelles via quality control pathways, such as mitophagy. Understanding the importance of motor proteins for mitochondrial homeostasis will help to elucidate the molecular basis of a number of human diseases. Show less
The intracellular functions of myosin motors requires a number of adaptor molecules, which control cargo attachment, but also fine-tune motor activity in time and space. These motor-adaptor-cargo inte Show more
The intracellular functions of myosin motors requires a number of adaptor molecules, which control cargo attachment, but also fine-tune motor activity in time and space. These motor-adaptor-cargo interactions are often weak, transient or highly regulated. To overcome these problems, we use a proximity labelling-based proteomics strategy to map the interactome of the unique minus end-directed actin motor MYO6. Detailed biochemical and functional analysis identified several distinct MYO6-adaptor modules including two complexes containing RhoGEFs: the LIFT (LARG-Induced F-actin for Tethering) complex that controls endosome positioning and motility through RHO-driven actin polymerisation; and the DISP (DOCK7-Induced Septin disPlacement) complex, a novel regulator of the septin cytoskeleton. These complexes emphasise the role of MYO6 in coordinating endosome dynamics and cytoskeletal architecture. This study provides the first Show less