title: The dynamics of the mitochondrial organelle as a potential therapeutic target.
abstract: Mitochondria play a central role in cell fate after stressors such as ischemic brain injury. The convergence of intracellular signaling pathways on mitochondria and their release of critical factors are now recognized as a default conduit to cell death or survival. Besides the individual processes that converge on or emanate from mitochondria, a mitochondrial organellar response to changes in the cellular environment has recently been described. Whereas mitochondria have previously been perceived as a major center for cellular signaling, one can postulate that the organelle's dynamics themselves affect cell survival. This brief perspective review puts forward the concept that disruptions in mitochondrial dynamics--biogenesis, clearance, and fission/fusion events--may underlie neural diseases and thus could be targeted as neuroprotective strategies in the context of ischemic injury. To do so, we present a general overview of the current understanding of mitochondrial dynamics and regulation. We then review emerging studies that correlate mitochondrial biogenesis, mitophagy, and fission/fusion events with neurologic disease and recovery. An overview of the system as it is currently understood is presented, and current assessment strategies and their limitations are discussed.
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University Shanghai Medical College, Shanghai, China. stetlerra@upmc.edu
authors.forename: R
authors.initials: R
authors.lastname: Anne Stetler
authors.forename: Rehana K
authors.initials: RK
authors.lastname: Leak
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Gao
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D051336:Mitochondrial Membranes / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D063306:Mitophagy / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D014463:Ultrasonography
chemical_list: D024101:Mitochondrial Proteins; D018696:Neuroprotective Agents