Autophagy as a second level protective process in conferring resistance to environmentally-induced oxidative stress
Autophagy as a second level protective process in conferring resistance to environmentally-induced oxidative stress
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DOI：
10.4161/auto.5528
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发表时间：
2008-02-16
期刊：
影响因子：
13.3
通讯作者：
Moore, Michael N.
中科院分区：
文献类型：
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作者：
Moore, Michael N.
这篇概念性论文以海洋软体动物（蓝色贻贝）为实验模型，探讨了溶酶体自噬在细胞防御环境诱导的氧化应激中的作用。有人提出，增强自噬清除氧化损伤的细胞器和蛋白质提供了针对氧化应激的第二级或多层防御。年龄色素或脂褐素是蛋白质和脂质氧化攻击的产物，可以在溶酶体中积聚，可能进一步产生活性氧 (ROS) 并抑制溶酶体功能，导致自噬失败。先前观察到的由营养剥夺引起的增强自噬对氧化应激的保护作用可以通过该模型来解释，其中自噬通过增强去除ROS损伤的蛋白质和细胞器来增强“细胞管家”，从而最大限度地减少潜在有害的应激/年龄色素的形成，并且已被提议作为一种抗衰老机制。最后，环境状况波动可能低水平触发贻贝自噬被认为是一种潜在的保护机制，有助于抵抗环境引起的氧化应激。进一步推测，在波动的环境中组成功能性生态组合（群落）的生物体，其中自噬的上调应提供选择性优势，可能被预先选择以耐受污染物诱导的氧化应激。
This conceptual paper addresses the role of lysosomal autophagy in cellular defense against environmentally-induced oxidative stress using a marine mollusc (the blue mussel) as an experimental model. It is proposed that augmented autophagic removal of oxidatively damaged organelles and proteins provides a second level or tier of defense against oxidative stress. Age pigment or lipofuscin is a product of oxidative attack on proteins and lipids and can accumulate in lysosomes, where it may generate further reactive oxygen species (ROS) and inhibit Iysosomal function, resulting in autophagic failure. The previously observed protective role of augmented autophagy, induced by nutritional deprivation, against oxidative stress can be explained by this model, where autophagy boosts "cellular housekeeping" through enhanced removal of ROS-damaged proteins and organelles minimizing formation of potentially harmful stress/age pigment, and has been proposed as an anti-aging mechanism. Finally, the probable low level triggering of autophagy in mussels by fluctuating environmental regimes is considered as a potential protective mechanism that will contribute to resistance to environmentally induced oxidative stress. It is further conjectured that organisms making up functional ecological assemblages (communities) in fluctuating environments, where upregulation of autophagy should provide a selective advantage, may be pre-selected to be tolerant of pollutant-induced oxidative stress.