Signaling pathways in mitochondrial dysfunction and aging.
Signaling pathways in mitochondrial dysfunction and aging.
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DOI：
10.1016/j.mad.2010.07.003
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发表时间：
2010-07
影响因子：
5.3
通讯作者：
Rizzuto, Rosario
中科院分区：
文献类型：
--
作者：
Mammucari, Cristina;Rizzuto, Rosario
线粒体是决定细胞生与死的核心角色。它们是能量产生所必需的，因为大多数细胞ATP是通过氧化磷酸化途径在其基质中产生的。同时，线粒体是凋亡性细胞死亡的主要调节因子，介导外源性（细胞表面受体介导的）和内源性凋亡途径。活性氧（ROS）作为电子传递链的副产物积累，导致线粒体损伤。非功能性线粒体在老年个体中积累，并且通过称为“线粒体自噬”的自噬过程去除受损的线粒体来维持细胞内稳态。此外，线粒体ROS代表导致自噬的信号分子，其包括胞质部分的大量降解。当细胞内稳态被扰乱，胞质组分被破坏时，自噬是一种防御机制，旨在清除无功能的蛋白质和细胞器。如果这还不够，则细胞死亡以与凋亡不同的形态学标志发生。这种二元选择整合了许多关键信息，这些信息集中在一些共同的监管要素上。在这篇综述中，重点将放在线粒体在自噬和细胞凋亡之间的交叉作用，突出信号通路和分子机制冲击这些细胞器。
Mitochondria are central players in the determination of cell life and death. They are essential for energy production, since most cellular ATP is produced in their matrix by the oxidative phosphorylation pathway. At the same time, mitochondria are the main regulators of apoptotic cell death, mediating both extrinsic (cell-surface receptor mediated) and intrinsic apoptotic pathways. Reactive oxygen species (ROS) accumulate as side products of the electron transport chain, causing mitochondrial damage. Non-functional mitochondria accumulate in aged individuals, and cell homeostasis is maintained by removing damaged mitochondria by an autophagic process called “mitophagy”. In addition, mitochondrial ROS represent signaling molecules leading to autophagy, consisting in the bulk degradation of cytosolic portions. When cell homeostasis is perturbed, and cytosolic components are damaged, autophagy represents a defense mechanism aimed at removing non functional proteins and organelles. If this is not sufficient, cell death occurs with distinct morphological hallmarks from apoptosis. This binary choice integrates a number of critical information converging on a number of common regulatory elements. In this review, the focus will be placed on the central role of mitochondria in the cross-talk between autophagy and apoptosis, highlighting the signaling pathways and molecular machinery impinging on these organelles.
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