title: Bcl-x L increases mitochondrial fission, fusion, and biomass in neurons.
abstract: Mitochondrial fission and fusion are linked to synaptic activity in healthy neurons and are implicated in the regulation of apoptotic cell death in many cell types. We developed fluorescence microscopy and computational strategies to directly measure mitochondrial fission and fusion frequencies and their effects on mitochondrial morphology in cultured neurons. We found that the rate of fission exceeds the rate of fusion in healthy neuronal processes, and, therefore, the fission/fusion ratio alone is insufficient to explain mitochondrial morphology at steady state. This imbalance between fission and fusion is compensated by growth of mitochondrial organelles. Bcl-x(L) increases the rates of both fusion and fission, but more important for explaining the longer organelle morphology induced by Bcl-x(L) is its ability to increase mitochondrial biomass. Deficits in these Bcl-x(L)-dependent mechanisms may be critical in neuronal dysfunction during the earliest phases of neurodegeneration, long before commitment to cell death.
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Berman
authors.forename: Ying-bei
authors.initials: YB
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Qi
authors.forename: J Michael
authors.initials: JM
authors.lastname: McCaffery
authors.forename: Edmund B
authors.initials: EB
authors.lastname: Rucker
authors.forename: Sandra
authors.initials: S
authors.lastname: Goebbels
authors.forename: Klaus-Armin
authors.initials: KA
authors.lastname: Nave
authors.forename: Beth A
authors.initials: BA
authors.lastname: Arnold
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Jonas
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Pineda
authors.forename: J Marie
authors.initials: JM
authors.lastname: Hardwick
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004734:Energy Metabolism / Q000235:genetics; D008561:Membrane Fusion / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence / Q000379:methods; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D051020:bcl-X Protein / Q000235:genetics*
chemical_list: C494812:Bcl2l1 protein, mouse; D051020:bcl-X Protein