mTORC2: a multifaceted regulator of autophagy.
Yanan SunHuihui WangTaiqi QuJunjie LuoPeng AnFazheng RenYongting LuoYi-Xuan LiPublished in: Cell communication and signaling : CCS (2023)
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. Video abstract.
Keyphrases
- cell death
- endoplasmic reticulum stress
- signaling pathway
- small molecule
- oxidative stress
- transcription factor
- cell proliferation
- dendritic cells
- intensive care unit
- risk assessment
- liver failure
- regulatory t cells
- gene expression
- genome wide
- climate change
- dna methylation
- respiratory failure
- mechanical ventilation
- aortic dissection