title: Mitochondria as a central sensor for axonal degenerative stimuli.
abstract: Axonal degeneration is a major contributor to neuronal dysfunction in many neurological conditions and has additional roles in development. It can be triggered by divergent stimuli including mechanical, metabolic, infectious, toxic, hereditary and inflammatory stresses. Axonal mitochondria are an important convergence point as regulators of bioenergetic metabolism, reactive oxygen species (ROS), Ca²⁺ homeostasis and protease activation. The challenges likely to render axonal mitochondria more vulnerable than their cellular counterparts are reviewed, including axonal transport, replenishing nuclear-encoded proteins and maintenance of quality control, fusion and fission in locations remote from the cell body. The potential for mitochondria to act as a decision node in axon loss is considered, highlighting the need to understand the biology of axonal mitochondria and their contributions to degenerative mechanisms for novel therapeutic strategies.
authors.affiliation: Millennium Nucleus for Regenerative Biology, Faculty of Biology, Catholic University of Chile, Santiago 8331150, Chile. fcourt@bio.puc.cl
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Court
authors.forename: Michael P
authors.initials: MP
authors.lastname: Coleman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D002118:Calcium