Department of Neurology.
Department of Pathology and Cell Biology, and.
J Clin Invest. 2019 Jan 2;129(1):34-45. doi: 10.1172/JCI120848.
Mitochondrial respiratory deficiencies have been observed in numerous neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. For decades, these reductions in oxidative phosphorylation (OxPhos) have been presumed to trigger an overall bioenergetic crisis in the neuron, resulting in cell death. While the connection between respiratory defects and neuronal death has never been proven, this hypothesis has been supported by the detection of nonspecific mitochondrial DNA mutations in these disorders. These findings led to the notion that mitochondrial respiratory defects could be initiators of these common neurodegenerative disorders, instead of being consequences of a prior insult, a theory we believe to be misconstrued. Herein, we review the roots of this mitochondrial hypothesis and offer a new perspective wherein mitochondria are analyzed not only from the OxPhos point of view, but also as a complex organelle residing at the epicenter of many metabolic pathways.
线粒体呼吸缺陷在许多神经退行性疾病中都有观察到，如阿尔茨海默病和帕金森病。几十年来，氧化磷酸化（OxPhos）的这些减少被认为会引发神经元的整体生物能量危机，导致细胞死亡。虽然呼吸缺陷与神经元死亡之间的联系从未得到证实，但这一假说得到了这些疾病中非特异性线粒体 DNA 突变检测的支持。这些发现导致了这样一种观点，即线粒体呼吸缺陷可能是这些常见神经退行性疾病的启动因素，而不是先前损伤的后果，我们认为这一理论被误解了。在此，我们回顾了这一线粒体假说的根源，并提出了一个新的观点，即不仅从 OxPhos 的角度，而且从线粒体作为位于许多代谢途径中心的复杂细胞器的角度来分析线粒体。
