Autophagy is a multi-step catabolic process that delivers cellular components to lysosomes for degradation and recycling. The dysregulation of this precisely controlled process disrupts cellular homeostasis and leads to many pathophysiological conditions. The mechanistic target of rapamycin (mTOR) is a central nutrient sensor that integrates growth signals with anabolism to fulfil biosynthetic and bioenergetic requirements. mTOR nucleates two distinct evolutionarily conserved complexes (mTORC1 and mTORC2). However, only mTORC1 is acutely inhibited by rapamycin. Consequently, mTORC1 is a well characterized regulator of autophagy. While less is known about mTORC2, the availability of acute small molecule inhibitors and multiple genetic models has led to increased understanding about the role of mTORC2 in autophagy. Emerging evidence suggests that the regulation of mTORC2 in autophagy is mainly through its downstream effector proteins, and is variable under different conditions and cellular contexts. Here, we review recent advances that describe a role for mTORC2 in this catabolic process, and propose that mTORC2 could be a potential clinical target for the treatment of autophagy-related diseases.

中文翻译：

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mTORC2：自噬的多方面调节因子

自噬是一个多步骤分解代谢过程，可将细胞成分输送到溶酶体进行降解和回收。这种精确控制过程的失调会破坏细胞稳态并导致许多病理生理状况。雷帕霉素 (mTOR) 的机制目标是一种中央营养传感器，它将生长信号与合成代谢相结合，以满足生物合成和生物能量的需求。mTOR 使两个不同的进化保守复合体（mTORC1 和 mTORC2）成核。然而，只有 mTORC1 被雷帕霉素强烈抑制。因此，mTORC1 是一种充分表征的自噬调节剂。虽然对 mTORC2 知之甚少，但急性小分子抑制剂和多种遗传模型的可用性使人们对 mTORC2 在自噬中的作用有了更多的了解。新出现的证据表明，mTORC2 在自噬中的调节主要是通过其下游效应蛋白，并且在不同条件和细胞环境下是可变的。在这里，我们回顾了描述 mTORC2 在此分解代谢过程中的作用的最新进展，并提出 mTORC2 可能是治疗自噬相关疾病的潜在临床靶点。