During autophagy mitochondria elongate, are spared from degradation and sustain cell viability.
During autophagy mitochondria elongate, are spared from degradation and sustain cell viability.
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DOI：
10.1038/ncb2220
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发表时间：
2011-05
影响因子：
21.3
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中科院分区：
文献类型：
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大量的细胞过程，包括凋亡，依赖于线粒体形状和超微结构的调节变化。我们很少了解线粒体的作用及其在自噬过程中的形态，自噬是真核细胞成分的大量降解和再循环过程。在这里，我们表明，线粒体形态决定了细胞对大自噬的反应。当自噬被触发时，线粒体在体外和体内伸长。饥饿时，细胞cAMP水平增加，蛋白激酶A（PKA）被激活。PKA反过来磷酸化促分裂动力蛋白相关蛋白1（DRP1），因此保留在细胞质中，导致不受阻碍的线粒体融合。延长的线粒体免于自噬降解，具有更多的嵴，增加ATP合酶的二聚化和活性，并维持ATP的产生。当延伸被遗传或代谢阻断时，线粒体反过来消耗ATP，加速饥饿诱导的死亡。因此，线粒体形态的调节变化决定了细胞在自噬过程中的命运。
A plethora of cellular processes, including apoptosis, depend on regulated changes in mitochondrial shape and ultrastructure. Scarce is our understanding of the role of mitochondria and of their morphology during autophagy, a bulk degradation and recycling process of eukaryotic cells’ constituents. Here we show that mitochondrial morphology determines the cellular response to macroautophagy. When autophagy is triggered, mitochondria elongate in vitro and in vivo. Upon starvation cellular cAMP levels increase and protein kinase A (PKA) becomes activated. PKA in turn phosphorylates the pro-fission dynamin related protein 1 (DRP1) that is therefore retained in the cytoplasm, leading to unopposed mitochondrial fusion. Elongated mitochondria are spared from autophagic degradation, possess more cristae, increase dimerization and activity of ATP synthase, and maintain ATP production. When elongation is genetically or pharmacologically blocked, mitochondria conversely consume ATP, precipitating starvation-induced death. Thus, regulated changes in mitochondrial morphology determine the fate of the cell during autophagy.