Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
EMBO J. 2013 Jul 3;32(13):1927-40. doi: 10.1038/emboj.2013.124. Epub 2013 May 28.
The chemical nature and functional significance of mitochondrial flashes associated with fluctuations in mitochondrial membrane potential is unclear. Using a ratiometric pH probe insensitive to superoxide, we show that flashes reflect matrix alkalinization transients of ∼0.4 pH units that persist in cells permeabilized in ion-free solutions and can be evoked by imposed mitochondrial depolarization. Ablation of the pro-fusion protein Optic atrophy 1 specifically abrogated pH flashes and reduced the propagation of matrix photoactivated GFP (paGFP). Ablation or invalidation of the pro-fission Dynamin-related protein 1 greatly enhanced flash propagation between contiguous mitochondria but marginally increased paGFP matrix diffusion, indicating that flashes propagate without matrix content exchange. The pH flashes were associated with synchronous depolarization and hyperpolarization events that promoted the membrane potential equilibration of juxtaposed mitochondria. We propose that flashes are energy conservation events triggered by the opening of a fusion pore between two contiguous mitochondria of different membrane potentials, propagating without matrix fusion to equilibrate the energetic state of connected mitochondria.
线粒体闪烁与线粒体膜电位波动相关的化学性质和功能意义尚不清楚。本研究使用一种对超氧自由基不敏感的比率 pH 探针，结果表明闪烁反映了约 0.4 pH 单位的基质碱化瞬间，该瞬间在离子自由溶液中透化的细胞中持续存在，并可被诱导的线粒体去极化引发。前融合蛋白视神经萎缩蛋白 1 的消融特异性地消除了 pH 闪烁并减少了基质光激活 GFP（paGFP）的传播。分裂相关蛋白 Dynamin-related protein 1 的消融或失效极大地增强了相邻线粒体之间的闪烁传播，但对 paGFP 基质扩散的影响较小，表明闪烁在没有基质内容物交换的情况下传播。pH 闪烁与同步去极化和超极化事件相关，促进了毗邻线粒体膜电位的平衡。我们提出，闪烁是由两个具有不同膜电位的相邻线粒体之间融合孔的打开触发的能量守恒事件，在没有基质融合的情况下传播，以平衡连接的线粒体的能量状态。
