title: The axonal transport of mitochondria.
abstract: Vigorous transport of cytoplasmic components along axons over substantial distances is crucial for the maintenance of neuron structure and function. The transport of mitochondria, which serves to distribute mitochondrial functions in a dynamic and non-uniform fashion, has attracted special interest in recent years following the discovery of functional connections among microtubules, motor proteins and mitochondria, and their influences on neurodegenerative diseases. Although the motor proteins that drive mitochondrial movement are now well characterized, the mechanisms by which anterograde and retrograde movement are coordinated with one another and with stationary axonal mitochondria are not yet understood. In this Commentary, we review why mitochondria move and how they move, focusing particularly on recent studies of transport regulation, which implicate control of motor activity by specific cell-signaling pathways, regulation of motor access to transport tracks and static microtubule-mitochondrion linkers. A detailed mechanism for modulating anterograde mitochondrial transport has been identified that involves Miro, a mitochondrial Ca(2+)-binding GTPase, which with associated proteins, can bind and control kinesin-1. Elements of the Miro complex also have important roles in mitochondrial fission-fusion dynamics, highlighting questions about the interdependence of biogenesis, transport, dynamics, maintenance and degradation.
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California, Cruz, CA 95060, USA. bsaxton@ucsc.edu
authors.forename: William M
authors.initials: WM
authors.lastname: Saxton
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hollenbeck
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004331:Drosophila melanogaster; D006801:Humans; D008561:Membrane Fusion; D008870:Microtubules / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D020409:Molecular Motor Proteins; C473124:RHOT1 protein, human; D020741:rho GTP-Binding Proteins; D002118:Calcium