Abstract

Eukaryotic cells frequently experience fluctuations of the external and internal environments, such as changes in nutrient, energy and oxygen sources, and protein folding status, which, after reaching a particular threshold, become a type of stress. Cells develop several ways to deal with these various types of stress to maintain homeostasis and survival. Among the cellular survival mechanisms, autophagy is one of the most critical ways to mediate metabolic adaptation and clearance of damaged organelles. Autophagy is maintained at a basal level under normal growing conditions and gets stimulated by stress through different but connected mechanisms. In this review, we summarize the advances in understanding the autophagy regulation mechanisms under multiple types of stress including nutrient, energy, oxidative, and ER stress in both yeast and mammalian systems.

Highlights

  • Eukaryotic cells frequently experience fluctuations of the external and internal environments, such as changes in nutrient, energy and oxygen sources, and protein folding status, which, after reaching a particular threshold, become a type of stress

  • We will summarize autophagy regulation mechanisms mediated by MTORC1 and briefly introduce some other molecules that contribute to autophagy regulation under nutrient stress

  • TFEB will be recruited to the lysosome by active RRAG GTPase and phosphorylated by MTORC1 [111], whereas starvation leads to a rapid translocation of TFEB from the cytosol to the nucleus and the induction of transcription of autophagy-associated genes such as UVRAG, WIPI, MAPLC3B, SQSTM1, VPS11, VPS18, and ATG9B [112]

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Summary

Overview of Autophagy in Yeast and Mammals

The basic mechanism of autophagy has been well-documented, and the entire process of autophagy can be divided into the following stages: induction and nucleation of the phagophore, expansion and maturation of the phagophore into a completed autophagosome, docking and fusion with the lysosome/vacuole, and degradation and efflux of the breakdown products (Figure 1A) [7]. The induction of autophagy begins at a single perivacuolar site, called the phagophore assembly site (PAS) which is proximal to the vacuole This step is regulated by the Atg protein complex, including Atg, Atg, and the Atg17-Atg31-Atg ternary subcomplex [10,11]. The second Ubl system involves Atg8-family proteins including MAP1LC3/LC3 and GABARAP subfamilies, undergoing a similar process With another protein, UVRAG, and core proteins from the PtdIns3K complex I, PtdIns3K complex II is formed, which is important for autophagy. Spliced XBP1 mRNA detection using ER stress-activated indicator” (ERAI) construct [49]

Mechanisms of Autophagy Regulation by Nutrient Stress in Yeast
Autophagy regulation by Gtr1-Gtr2
Autophagy Regulation in Mammalian Cells
Autophagy Regulation by MTORC1
Other Autophagy Regulation during Nutrient Stress
Autophagy Regulation under Energy Stress
Mechanisms of Autophagy Regulation by Oxidative Stress in Yeast
Mechanisms of Autophagy Regulation by Oxidative Stress in Mammalian Cells
Mechanisms of Autophagy Regulation by Nitrosative Stress
Endoplasmic Reticulum Stress and Autophagy
The Mechanisms of ER Stress-Mediated Autophagy in Yeast
The Mechanisms of ER Stress-Mediated Autophagy in Mammalian Cells
EIF2AK3
Calcium
Conclusions
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