Department of Biochemistry, University of Colorado, Boulder, CO.
Howard Hughes Medical Institute, Chevy Chase, MD.
J Cell Biol. 2020 Apr 6;219(4). doi: 10.1083/jcb.201911122.
The steady-state morphology of the mitochondrial network is maintained by a balance of constitutive fission and fusion reactions. Disruption of this steady-state morphology results in either a fragmented or elongated network, both of which are associated with altered metabolic states and disease. How the processes of fission and fusion are balanced by the cell is unclear. Here we show that mitochondrial fission and fusion are spatially coordinated at ER membrane contact sites (MCSs). Multiple measures indicate that the mitochondrial fusion machinery, Mitofusins, accumulate at ER MCSs where fusion occurs. Furthermore, fission and fusion machineries colocalize to form hotspots for membrane dynamics at ER MCSs that can persist through sequential events. Because these hotspots can undergo fission and fusion, they have the potential to quickly respond to metabolic cues. Indeed, we discover that ER MCSs define the interface between polarized and depolarized segments of mitochondria and can rescue the membrane potential of damaged mitochondria by ER-associated fusion.
线粒体网络的稳态形态由组成性分裂和融合反应的平衡维持。这种稳态形态的破坏会导致网络碎片化或拉长，这两者都与代谢状态的改变和疾病有关。细胞如何平衡分裂和融合过程尚不清楚。在这里，我们表明线粒体分裂和融合在 ER 膜接触位点（MCS）处是空间协调的。多项措施表明，线粒体融合机制，即线粒体融合蛋白，在发生融合的 ER MCS 处积累。此外，分裂和融合机制在 ER MCS 处共定位，形成膜动力学热点，这些热点可以通过连续的事件持续存在。因为这些热点可以发生分裂和融合，所以它们有可能快速响应代谢信号。事实上，我们发现 ER MCS 定义了极化和去极化线粒体段之间的界面，并可以通过与 ER 相关的融合来挽救受损线粒体的膜电位。
