Berman Sarah B, Chen Ying-bei, Qi Bing, McCaffery J Michael, Rucker Edmund B, Goebbels Sandra, Nave Klaus-Armin, Arnold Beth A, Jonas Elizabeth A, Pineda Fernando J, Hardwick J Marie
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
J Cell Biol. 2009 Mar 9;184(5):707-19. doi: 10.1083/jcb.200809060. Epub 2009 Mar 2.
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.
线粒体的分裂与融合与健康神经元中的突触活动相关联，并且在多种细胞类型的凋亡性细胞死亡调控中发挥作用。我们开发了荧光显微镜和计算策略，以直接测量培养神经元中线粒体的分裂与融合频率及其对线粒体形态的影响。我们发现，在健康的神经元突起中，分裂速率超过融合速率，因此，仅靠分裂/融合比不足以解释稳态下的线粒体形态。线粒体细胞器的生长可补偿分裂与融合之间的这种失衡。Bcl-x(L)可提高融合和分裂的速率，但对于解释由Bcl-x(L)诱导的更长的细胞器形态而言，更重要的是其增加线粒体生物量的能力。在神经退行性变的最早阶段，早在细胞死亡发生之前，这些依赖Bcl-x(L)的机制出现缺陷可能是神经元功能障碍的关键因素。
