Advances in Autophagy Regulatory Mechanisms.
Advances in Autophagy Regulatory Mechanisms.
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作者：
Gallagher LE;Williamson LE;Chan EY
当受到有限营养的挑战时，自噬通过降解和回收内部成分，在细胞代谢中发挥着关键作用。这种基本且保守的机制基于膜运输途径，其中新生自噬体吞噬细胞质货物形成囊泡，将其内容物运输到溶酶体进行降解。基于这个简单的方案，自噬调节细胞代谢和细胞质质量控制，从而影响正常哺乳动物生理学和病理生理学的广泛范围。在这篇综述中，我们总结了自噬调控三个广泛领域的最新进展。我们讨论了自噬体如何从内源性膜启动的当前模型。我们详细介绍了不协调的 51 样激酶 (ULK) 复合物如何在雷帕霉素复合物 1 (MTORC1) 机械靶点下游被激活。最后，我们总结了可以感知氨基酸可用性从而导致 MTORC1 激活的上游信号机制。
Autophagy plays a critical role in cell metabolism by degrading and recycling internal components when challenged with limited nutrients. This fundamental and conserved mechanism is based on a membrane trafficking pathway in which nascent autophagosomes engulf cytoplasmic cargo to form vesicles that transport their content to the lysosome for degradation. Based on this simple scheme, autophagy modulates cellular metabolism and cytoplasmic quality control to influence an unexpectedly wide range of normal mammalian physiology and pathophysiology. In this review, we summarise recent advancements in three broad areas of autophagy regulation. We discuss current models on how autophagosomes are initiated from endogenous membranes. We detail how the uncoordinated 51-like kinase (ULK) complex becomes activated downstream of mechanistic target of rapamycin complex 1 (MTORC1). Finally, we summarise the upstream signalling mechanisms that can sense amino acid availability leading to activation of MTORC1.