mTORC2: a multifaceted regulator of autophagy

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.

Automated summary

Autophagy is a highly regulated catabolic process involving the degradation and recycling of cellular components. The mechanistic target of rapamycin (mTOR) plays a central role in autophagy regulation. While mTORC1 is well-studied and known to be acutely inhibited by rapamycin, less is known about mTORC2. Recent research suggests that mTORC2's role in autophagy is mainly through its downstream effector proteins and varies under different conditions and cellular contexts. Understanding the involvement of mTORC2 in autophagy could potentially lead to new treatment strategies for autophagy-related diseases.