A host of actin-binding proteins regulate filament dynamics and the assembly into higher-ordered structures, such as stress fibres, lamellipodia, filopodia and actin networks associated with the plasma membrane or intracellular membranes ( Rottner et al., 2017). Myosin motors translocate along actin filamentsĪctin monomers polymerize to form actin filaments. Interestingly, Miro1/2 without TRAK1/2 can also recruit myosin of class XIX (MYO19) to mitochondria ( Bocanegra et al., 2020a).īox 1. The key adaptor complex linking kinesin-1 and dynein to mitochondria consists of Miro1 or Miro2 (referred to collectively as Miro1/2 also known as RHOT1 or RHOT2, respectively) and trafficking kinesin protein 1 or 2 (TRAK1 or TRAK2, referred to collectively as TRAK1/2), and is hereafter referred to as the Miro–TRAK complex ( Eberhardt et al., 2020 Melkov and Abdu, 2018). The overall control of mitochondrial homeostasis involves three types of motor proteins that translocate along cytoskeletal tracks: myosins moving along actin filaments ( Box 1), as well as kinesins and dynein moving along microtubules (MTs Box 2 Vale and Milligan, 2000). Indeed, defects in mitochondrial homeostasis manifesting as fission–fusion imbalance, impaired transport or reduced clearance of faulty mitochondria by mitophagy increase with age and can lead to a wide range of neurodegenerative disorders ( Bakula and Scheibye-Knudsen, 2020 Seo et al., 2010 Sleigh et al., 2019 Tilokani et al., 2018). To maintain organellar homeostasis, mitochondria constantly remodel their network through fission and fusion events, reposition themselves through motor protein- and cytoskeleton-dependent transport, and finally are degraded via several quality control mechanisms ( Chan, 2020 Harper et al., 2018 Sleigh et al., 2019). Mitochondria can sense stress stimuli, such as nutrient deprivation, and the overall metabolic state of the cell ( Chandel, 2015 Giacomello et al., 2020). The intermembrane space (IMS) is sandwiched between the OMM and IMM. Mitochondria are double-membraned organelles of endosymbiotic origin that have an outer mitochondrial membrane (OMM) facing the cytosol and an inner mitochondrial membrane (IMM) marking the boundary of the mitochondrial matrix, which contains the mitochondrial DNA (mtDNA). In addition to producing energy, they also play critical roles in the biosynthesis of macromolecules, Ca 2 + homeostasis, and signalling in programmed cell death and immunity. Mitochondria are the powerhouses of the cell, generating adenosine triphosphate (ATP) by oxidative phosphorylation (OXPHOS). Understanding the importance of motor proteins for mitochondrial homeostasis will help to elucidate the molecular basis of a number of human diseases. 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. 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. 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. 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 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. Mitochondria are multifunctional organelles that not only produce energy for the cell, but are also important for cell signalling, apoptosis and many biosynthetic pathways.
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