The impact of autophagy on cell death modalities.
The impact of autophagy on cell death modalities.
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DOI：
10.1155/2014/502676
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发表时间：
2014
影响因子：
--
通讯作者：
Choi AM
中科院分区：
文献类型：
--
作者：
Ryter SW;Mizumura K;Choi AM
自噬是细胞器和蛋白质通过溶酶体依赖的降解途径周转的一种动态平衡的细胞机制。在饥饿过程中，自噬通过代谢前体的循环促进细胞存活。此外，自噬可以调节其他重要过程，如程序性细胞死亡(如细胞凋亡)、炎症和获得性免疫机制，从而影响疾病的发病机制。选择性途径可以针对不同的货物(例如线粒体和蛋白质)进行自噬降解。目前，自噬与各种形式的调控或非调控的细胞死亡之间的因果关系尚不清楚。自噬可能与caspase抑制引发的坏死样细胞死亡有关。自噬和凋亡已被证明是一致的或拮抗的，取决于实验背景，并在信号转导元件之间共享串扰。自噬可以调节其他调节形式的细胞死亡的结果，如坏死性下垂。最近的研究表明，自噬可以抑制炎症反应，包括炎症体依赖的caspase-1激活和致炎细胞因子的成熟。自噬也可能是caspase-1依赖的细胞死亡(下垂)的调节因子。旨在调节自噬的策略可能导致对一些疾病的治疗干预，在这些疾病中，细胞凋亡或其他形式的受调控的细胞死亡可能发挥关键作用。
Autophagy represents a homeostatic cellular mechanism for the turnover of organelles and proteins, through a lysosome-dependent degradation pathway. During starvation, autophagy facilitates cell survival through the recycling of metabolic precursors. Additionally, autophagy can modulate other vital processes such as programmed cell death (e.g., apoptosis), inflammation, and adaptive immune mechanisms and thereby influence disease pathogenesis. Selective pathways can target distinct cargoes (e.g., mitochondria and proteins) for autophagic degradation. At present, the causal relationship between autophagy and various forms of regulated or nonregulated cell death remains unclear. Autophagy can occur in association with necrosis-like cell death triggered by caspase inhibition. Autophagy and apoptosis have been shown to be coincident or antagonistic, depending on experimental context, and share cross-talk between signal transduction elements. Autophagy may modulate the outcome of other regulated forms of cell death such as necroptosis. Recent advances suggest that autophagy can dampen inflammatory responses, including inflammasome-dependent caspase-1 activation and maturation of proinflammatory cytokines. Autophagy may also act as regulator of caspase-1 dependent cell death (pyroptosis). Strategies aimed at modulating autophagy may lead to therapeutic interventions for diseases in which apoptosis or other forms of regulated cell death may play a cardinal role.