Loss of Mitochondrial Function Impairs Lysosomes
Loss of Mitochondrial Function Impairs Lysosomes
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DOI：
10.1074/jbc.m115.695825
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发表时间：
2016-05-06
影响因子：
4.8
通讯作者：
Germain, Marc
中科院分区：
文献类型：
--
作者：
Demers-Lamarche, Julie;Guillebaud, Gerald;Germain, Marc
如在神经退行性疾病中观察到的，线粒体功能的改变导致能量代谢中断和破坏性活性氧的产生。在这里，我们证明，线粒体功能障碍也破坏了溶酶体的结构和功能，主要的降解和回收细胞器。具体而言，在线粒体蛋白AIF、OPA 1或PINK 1缺失后，线粒体功能的抑制以及电子传递链的化学抑制损害了溶酶体活性并导致大溶酶体空泡的出现。重要的是，我们的研究结果表明，溶酶体损伤依赖于活性氧。鉴于线粒体功能和溶酶体活性的改变是神经退行性疾病的关键特征，这项工作为神经退行性疾病的病因学提供了重要的见解。
Alterations in mitochondrial function, as observed in neurodegenerative diseases, lead to disrupted energy metabolism and production of damaging reactive oxygen species. Here, we demonstrate that mitochondrial dysfunction also disrupts the structure and function of lysosomes, the main degradation and recycling organelle. Specifically, inhibition of mitochondrial function, following deletion of the mitochondrial protein AIF, OPA1, or PINK1, as well as chemical inhibition of the electron transport chain, impaired lysosomal activity and caused the appearance of large lysosomal vacuoles. Importantly, our results show that lysosomal impairment is dependent on reactive oxygen species. Given that alterations in both mitochondrial function and lysosomal activity are key features of neurodegenerative diseases, this work provides important insights into the etiology of neurodegenerative diseases.