How Cells Deal with the Fluctuating Environment: Autophagy Regulation under Stress in Yeast and Mammalian Systems
Abstract
:1. Overview of Autophagy in Yeast and Mammals
2. Autophagy Regulation under Nutrient Stress
2.1. Mechanisms of Autophagy Regulation by Nutrient Stress in Yeast
2.2. Autophagy Regulation in Mammalian Cells
2.2.1. Autophagy Regulation by MTORC1
2.2.2. Other Autophagy Regulation during Nutrient Stress
3. Autophagy Regulation under Energy Stress
4. Autophagy Regulation under Oxidative/Nitrosative Stress
4.1. Mechanisms of Autophagy Regulation by Oxidative Stress in Yeast
4.2. Mechanisms of Autophagy Regulation by Oxidative Stress in Mammalian Cells
4.3. Mechanisms of Autophagy Regulation by Nitrosative Stress
5. Autophagy Regulation under ER Stress
5.1. Endoplasmic Reticulum Stress and Autophagy
5.2. The Mechanisms of ER Stress-Mediated Autophagy in Yeast
5.3. The Mechanisms of ER Stress-Mediated Autophagy in Mammalian Cells
5.3.1. ERN1
5.3.2. EIF2AK3
5.3.3. ATF6
5.3.4. Calcium
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AMPK | AMP-activated protein kinase |
ATG | autophagy related |
ER | endoplasmic reticulum |
ERAD | ER-associated degradation |
GAP | GTPase activating protein |
H2O2 | hydrogen peroxide |
m6A | N6-methyl-adenosine |
MTORC1 | mechanistic target of rapamycin kinase complex 1 |
NO | nitric oxide |
PAS | phagophore assembly site |
PE | phosphatidylethanolamine |
PtdIns3K | class III phosphatidylinositol kinase |
RNS | reactive nitrogen species |
ROS | reactive oxygen species |
TFs | transcription factors |
Ubl | ubiquitin-like |
UPR | unfolded protein response |
V-ATPase | vacuolar-type H+-translocating ATPase |
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Stress Type | Organism | Biomarkers | Detection | Reference |
---|---|---|---|---|
Nutrient stress | Yeast | TORC1 inactivation | Sch9 dephosphorylation | [27] |
Mammalian EIF4EBP1 dephosphorylation in vitro | [28] | |||
Mammals | MTORC1 inactivation | RPS6KB1 dephosphorylation | [29] | |
EIF4EBP1 dephosphorylation | [29] | |||
Energy stress | Yeast and mammals | Lower ATP: ADP/AMP ratio | Liquid chromatography to detect ATP, ADP and AMP level | [30] |
ATP:ADP fluorescence reporter | [31,32] | |||
Bioluminescent detection | [33] | |||
Yeast | Snf1 activation | “SAMS” peptide phosphorylation | [34] | |
Mammals | AMPK activation | AMPK phosphorylation | [35] | |
Phosphorylation of downstream targets such as ACAC (acetyl-CoA carboxylase) | [35] | |||
Oxidative stress | Yeast and Mammals | High level of ROS | Dichlorodihydrofluorescein fluorescence | [36] |
PG1 or PC1 fluorescence | [37] | |||
Calcein-acetoxymethylester (calcein-AM) fluorescence | [38] | |||
CellROX dye | [39] | |||
Increased GSSG:GSH ratio | High-performance liquid chromatography | [40] | ||
Capillary electrophoresis | [40] | |||
Bioluminescence | [41] | |||
Genetically-encoded fluorescent sensors | [42,43] | |||
Lipid peroxidation | Fluorescence shift of C11-BODIPY (581/591) | [44] | ||
TBA-MDA assay | [45,46] | |||
ER stress | Yeast | Misfolded protein accumulation | Kar2 sedimentation | [47] |
UPR pathway activation | Transcription reporter containing a UPR element promoter driving fluorescent proteins | [47] | ||
Ire1 clustering | [47] | |||
Mammals | Protein aggregates | Thioflavin T (ThT) fluorescence | [48] | |
UPR pathway activation | Spliced XBP1 mRNA detection using ER stress-activated indicator” (ERAI) construct | [49] | ||
Upregulated expression of UPR target genes, including DDIT3 and HSPA5/GRP78 | [50] | |||
ATF6 translocation | [51] |
Type of Regulation | Regulatory Factors | Conditions | Effects (↑, Positive; ↓, Negative) | Target Genes or Proteins | Reference | |
---|---|---|---|---|---|---|
Transcriptional regulation | Pho23 | Nutrient-rich | ↓ | ATG1, 7, 8, 9, 12, 14, 29 | [69] | |
Spt10 | Nutrient-rich | ↓ | ATG1, 7, 9,14, 32 | [62] | ||
Fyv5 | Nutrient-rich and starvation | ↓ | ATG1, 7, 8, 9,14, 29, 32 | |||
Sfl1 | Nutrient-rich | ↓ | ATG1, 7, 8, 9, 14, 29, 32 | |||
Sko1 | Nutrient-rich and starvation | ↓ | ATG1, 7, 8, 32 | |||
Zap1 | Nutrient-rich | ↓ | ATG1, 7, 8, 9, 14, 29, 32 | |||
Swi5 | Nutrient-rich | ↑ | ATG7, 8, 9, 14, 29 | |||
Rsc1 | Starvation | ↑ | ATG8 | [70] | ||
Spt4/5 | Nutrient-rich | ↓ | ATG8, 41 | [71] | ||
Starvation | ↑ | ATG41 | ||||
Post-transcriptional regulation | Xrn1 | Nutrient-rich | ↓ | ATG1, 4, 5, 7, 8, 12, 14, 16, 29, 31 | [72] | |
Dhh1 | Nutrient-rich | ↓ | ATG3, 7, 8, 19, 20, 22, 24 | [68] | ||
Starvation | ↑ | ATG1,13 | [73] | |||
Pat1 | Starvation | ↑ | ATG1, 2,7, 9 | [74] | ||
Psp2 | Starvation | ↑ | ATG1, 13 | [75] | ||
Ded1 | Starvation | ↑ | ATG1 | [76] | ||
Post- translational regulation | Phosphorylation | Hrr25 | Cvt pathway and pexophagy induction | ↑ | Atg19,36 | [77] |
Ubiquitination | Met30 | Nutrient-rich | ↓ | Atg9 | [78] | |
Acetylation | Esa1 | Starvation | ↑ | Atg3 | [79] | |
Deacetylation | Rpd3 | Starvation | ↓ | Atg3 | [79] | |
Epigenetic regulation | Acetylation | Sas2 | Nutrient-rich | ↓ | Histone H4 Lys16 | [80] |
Methylation | Unclear | Nutrient-rich | ↓ | Histone H3 Lys4 | [80] |
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Lei, Y.; Huang, Y.; Wen, X.; Yin, Z.; Zhang, Z.; Klionsky, D.J. How Cells Deal with the Fluctuating Environment: Autophagy Regulation under Stress in Yeast and Mammalian Systems. Antioxidants 2022, 11, 304. https://doi.org/10.3390/antiox11020304
Lei Y, Huang Y, Wen X, Yin Z, Zhang Z, Klionsky DJ. How Cells Deal with the Fluctuating Environment: Autophagy Regulation under Stress in Yeast and Mammalian Systems. Antioxidants. 2022; 11(2):304. https://doi.org/10.3390/antiox11020304
Chicago/Turabian StyleLei, Yuchen, Yuxiang Huang, Xin Wen, Zhangyuan Yin, Zhihai Zhang, and Daniel J. Klionsky. 2022. "How Cells Deal with the Fluctuating Environment: Autophagy Regulation under Stress in Yeast and Mammalian Systems" Antioxidants 11, no. 2: 304. https://doi.org/10.3390/antiox11020304
APA StyleLei, Y., Huang, Y., Wen, X., Yin, Z., Zhang, Z., & Klionsky, D. J. (2022). How Cells Deal with the Fluctuating Environment: Autophagy Regulation under Stress in Yeast and Mammalian Systems. Antioxidants, 11(2), 304. https://doi.org/10.3390/antiox11020304