MIRO-1 决定 GPCR 激活和钙应激时线粒体的形状转变。
MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca Stress.
机构信息
Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Department of Anatomy and Cell Biology, Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
出版信息
Cell Rep. 2018 Apr 24;23(4):1005-1019. doi: 10.1016/j.celrep.2018.03.098.
Mitochondria shape cytosolic calcium ([Ca]) transients and utilize the mitochondrial Ca ([Ca]) in exchange for bioenergetics output. Conversely, dysregulated [Ca] causes [Ca] overload and induces permeability transition pore and cell death. Ablation of MCU-mediated Ca uptake exhibited elevated [Ca] and failed to prevent stress-induced cell death. The mechanisms for these effects remain elusive. Here, we report that mitochondria undergo a cytosolic Ca-induced shape change that is distinct from mitochondrial fission and swelling. [Ca] elevation, but not MCU-mediated Ca uptake, appears to be essential for the process we term mitochondrial shape transition (MiST). MiST is mediated by the mitochondrial protein Miro1 through its EF-hand domain 1 in multiple cell types. Moreover, Ca-dependent disruption of Miro1/KIF5B/tubulin complex is determined by Miro1 EF1 domain. Functionally, Miro1-dependent MiST is essential for autophagy/mitophagy that is attenuated in Miro1 EF1 mutants. Thus, Miro1 is a cytosolic Ca sensor that decodes metazoan Ca signals as MiST.
线粒体塑造细胞质钙离子（[Ca]）瞬变，并利用线粒体钙（[Ca]）进行能量代谢输出。相反，[Ca]失调会导致[Ca]过载，诱导通透性转换孔和细胞死亡。MCU 介导的 Ca 摄取的缺失会导致[Ca]升高，并不能预防应激诱导的细胞死亡。这些影响的机制仍不清楚。在这里，我们报告说，线粒体经历了一种不同于线粒体裂变和肿胀的细胞质 Ca 诱导的形状变化。[Ca]的升高，而不是 MCU 介导的 Ca 摄取，似乎是我们称之为线粒体形状转变（MiST）的过程所必需的。MiST 是由线粒体蛋白 Miro1 通过其在多种细胞类型中的 EF 手结构域 1 介导的。此外，Ca 依赖性的 Miro1/KIF5B/微管蛋白复合物的破坏是由 Miro1 EF1 结构域决定的。在功能上，Miro1 依赖性的 MiST 对于自噬/线粒体自噬是必需的，而在 Miro1 EF1 突变体中，自噬/线粒体自噬会减弱。因此，Miro1 是一种细胞质 Ca 传感器，可将后生动物 Ca 信号解码为 MiST。
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