The mTOR–Autophagy Axis and the Control of Metabolism

Abstract

The mechanistic target of rapamycin (mTOR), master regulator of cellular metabolism, exists in two distinct complexes: mTOR complex 1 and mTOR complex 2 (mTORC1 and 2). MTORC1 is a master switch for most energetically onerous processes in the cell, driving cell growth and building cellular biomass in instances of nutrient sufficiency, and conversely, allowing autophagic recycling of cellular components upon nutrient limitation. The means by which the mTOR kinase blocks autophagy include direct inhibition of the early steps of the process, and the control of the lysosomal degradative capacity of the cell by inhibiting the transactivation of genes encoding structural, regulatory, and catalytic factors. Upon inhibition of mTOR, autophagic recycling of cellular components results in the reactivation of mTORC1; thus, autophagy lies both downstream and upstream of mTOR. The functional relationship between the mTOR pathway and autophagy involves complex regulatory loops that are significantly deciphered at the cellular level, but incompletely understood at the physiological level. Nevertheless, genetic evidence stemming from the use of engineered strains of mice has provided significant insight into the overlapping and complementary metabolic effects that physiological autophagy and the control of mTOR activity exert during fasting and nutrient overload.

Baicalin improves the functions of granulosa cells and the ovary in aged mice through the mTOR signaling pathway

“…mTOR is a serine/threonine kinase and an important cell regulator, which can regulate cell growth and proliferation in response to a variety of signals, and it plays an especially vital role in regulating autophagy [ 44 ]. mTOR is a highly evolved kinase whose catalytic core is composed of two different complexes, mTORC1 and mTORC2 [ 45 ]. Yu et al (2021) found that Qingfei oral liquid (QF) could participate in the regulation of autophagy through the mTOR signaling pathway to reduce the inflammation caused by respiratory syncytial virus (RSV) infection in asthmatic mice [ 46 ].…”

Identification of Three Potential Prognostic Genes in Platinum-Resistant Ovarian Cancer via Integrated Bioinformatics Analysis

“…The mTORC1 pathway plays a central role in the regulation of growth and metabolism in eukaryotic cells, affecting anabolism, autophagy and catabolism. 44 In addition, mTORC1 can also regulate mitochondrial metabolism, standing as an important regulator of mitochondrial function. 45 John T's study found that mTOR can regulate For personal use only.…”

FoxO transcription factors in mitochondrial homeostasis

“…As a target of FoxOs, Tfeb regulates autophagosomal and lysosomal genes as well as the fusion of autophagosome with lysosome [96][97][98]. Tfeb activity is controlled by posttranslational modification, such as mTORC1 mediated phosphorylation that excludes Tfeb from the nucleus [99][100][101]. At transcriptional level, Tfeb gene was transactivated by FoxO1, which might account for mitophagy regulation and white-beige adipose tissue conversion [95].…”