Bcl-xL increases mitochondrial fission, fusion, and biomass in neurons

被引:175
作者
Berman, Sarah B. [1 ,3 ,5 ]
Chen, Ying-bei [4 ]
Qi, Bing [1 ]
McCaffery, J. Michael [6 ,7 ]
Rucker, Edmund B., III [8 ]
Goebbels, Sandra [9 ]
Nave, Klaus-Armin [9 ]
Arnold, Beth A. [5 ]
Jonas, Elizabeth A. [10 ]
Pineda, Fernando J. [1 ,2 ]
Hardwick, J. Marie [1 ,3 ,4 ]
机构
[1] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA
[3] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA
[5] Univ Pittsburgh, Pittsburgh Inst Neurodegenerat Dis, Dept Neurol, Pittsburgh, PA 15260 USA
[6] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA
[7] Johns Hopkins Univ, Integrated Imaging Ctr, Baltimore, MD 21218 USA
[8] Univ Missouri, Anim Sci Unit, Columbia, MO 65211 USA
[9] Max Planck Inst Expt Med, Dept Neurogenet, D-37075 Gottingen, Germany
[10] Yale Univ, Dept Internal Med, New Haven, CT 06520 USA
基金
美国国家卫生研究院;
关键词
PROGRAMMED CELL-DEATH; OUTER-MEMBRANE PERMEABILIZATION; CULTURED HIPPOCAMPAL-NEURONS; CYTOCHROME-C RELEASE; SYNAPTIC-TRANSMISSION; PHOTOACTIVATABLE GFP; PEROXISOMAL FISSION; MAMMALIAN-CELLS; BCL-XL; APOPTOSIS;
D O I
10.1083/jcb.200809060
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:707 / 719
页数:13
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