Transcriptional Regulation of Autophagy and Its Implications in Human Disease

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2023 Apr 12

PMID 37045910

Authors

Yuchen Lei

Daniel J Klionsky

Affiliations

Soon will be listed here.

Abstract

Macroautophagy/autophagy is a conserved catabolic pathway that is vital for maintaining cell homeostasis and promoting cell survival under stressful conditions. Dysregulation of autophagy is associated with a variety of human diseases, such as cancer, neurodegenerative diseases, and metabolic disorders. Therefore, this pathway must be precisely regulated at multiple levels, involving epigenetic, transcriptional, post-transcriptional, translational, and post-translational mechanisms, to prevent inappropriate autophagy activity. In this review, we focus on autophagy regulation at the transcriptional level, summarizing the transcription factors that control autophagy gene expression in both yeast and mammalian cells. Because the expression and/or subcellular localization of some autophagy transcription factors are altered in certain diseases, we also discuss how changes in transcriptional regulation of autophagy are associated with human pathophysiologies.

Citing Articles

2,4-Dinitrophenol is toxic on a low caloric diet but extends lifespan of Drosophila melanogaster on nutrient-rich diets without an impact on metabolism.

Strilbytska O, Semaniuk U, Yurkevych I, Berezovskyi V, Glovyak A, Gospodaryov D Biogerontology. 2024; 26(1):27.

PMID: 39702849 DOI: 10.1007/s10522-024-10169-9.

Enhancement of Autophagy in Macrophages via the p120-Catenin-Mediated mTOR Signaling Pathway.

Kanmani S, Song X, Kanmani P, Wu X, Tan X, Liu J J Immunol. 2024; 213(11):1666-1675.

PMID: 39423222 PMC: 11610512. DOI: 10.4049/jimmunol.2400189.

Role of canonical and noncanonical autophagy pathways in shaping the life journey of B cells.

Wang Y, Wu L, Van Kaer L Front Immunol. 2024; 15:1426204.

PMID: 39139569 PMC: 11319164. DOI: 10.3389/fimmu.2024.1426204.

RAB37-mediated autophagy guards ovarian homeostasis and function.

Xu X, Hu M, Ying R, Zou J, Du Z, Lin L Autophagy. 2024; 20(12):2738-2751.

PMID: 39113565 PMC: 11587855. DOI: 10.1080/15548627.2024.2389568.

Autophagy and hepatic lipid metabolism: mechanistic insight and therapeutic potential for MASLD.

Raza S, Rajak S, Yen P, Sinha R NPJ Metab Health Dis. 2024; 2(1):19.

PMID: 39100919 PMC: 11296953. DOI: 10.1038/s44324-024-00022-5.

References

Huang T, Jiang G, Zhang Y, Lei Y, Liu S, Li H . The RNA polymerase II subunit Rpb9 activates ATG1 transcription and autophagy. EMBO Rep. 2022; 23(11):e54993. PMC: 9638876. DOI: 10.15252/embr.202254993. View

Hoshino A, Mita Y, Okawa Y, Ariyoshi M, Iwai-Kanai E, Ueyama T . Cytosolic p53 inhibits Parkin-mediated mitophagy and promotes mitochondrial dysfunction in the mouse heart. Nat Commun. 2013; 4:2308. DOI: 10.1038/ncomms3308. View

Yu F, Imamura Y, Ueno M, Suzuki S, Ohsumi Y, Yukawa M . The yeast chromatin remodeler Rsc1-RSC complex is required for transcriptional activation of autophagy-related genes and inhibition of the TORC1 pathway in response to nitrogen starvation. Biochem Biophys Res Commun. 2015; 464(4):1248-1253. DOI: 10.1016/j.bbrc.2015.07.114. View

Yang J, Xu H, Zhang C, Yang X, Cai W, Chen X . A prion-like domain of TFEB mediates the co-aggregation of TFEB and mHTT. Autophagy. 2022; 19(2):544-550. PMC: 9851196. DOI: 10.1080/15548627.2022.2083857. View

Margariti A, Li H, Chen T, Martin D, Vizcay-Barrena G, Alam S . XBP1 mRNA splicing triggers an autophagic response in endothelial cells through BECLIN-1 transcriptional activation. J Biol Chem. 2012; 288(2):859-72. PMC: 3543035. DOI: 10.1074/jbc.M112.412783. View

Fimia G, Stoykova A, Romagnoli A, Giunta L, Di Bartolomeo S, Nardacci R . Ambra1 regulates autophagy and development of the nervous system. Nature. 2007; 447(7148):1121-5. DOI: 10.1038/nature05925. View

Brady O, Martina J, Puertollano R . Emerging roles for TFEB in the immune response and inflammation. Autophagy. 2017; 14(2):181-189. PMC: 5902167. DOI: 10.1080/15548627.2017.1313943. View

Copetti T, Bertoli C, Dalla E, Demarchi F, Schneider C . p65/RelA modulates BECN1 transcription and autophagy. Mol Cell Biol. 2009; 29(10):2594-608. PMC: 2682036. DOI: 10.1128/MCB.01396-08. View

Sakamaki J, Wilkinson S, Hahn M, Tasdemir N, OPrey J, Clark W . Bromodomain Protein BRD4 Is a Transcriptional Repressor of Autophagy and Lysosomal Function. Mol Cell. 2017; 66(4):517-532.e9. PMC: 5446411. DOI: 10.1016/j.molcel.2017.04.027. View

10.

Tremblay M, Sanchez-Ferras O, Bouchard M . GATA transcription factors in development and disease. Development. 2018; 145(20). DOI: 10.1242/dev.164384. View

11.

Nascimbeni A, Codogno P, Morel E . Phosphatidylinositol-3-phosphate in the regulation of autophagy membrane dynamics. FEBS J. 2016; 284(9):1267-1278. DOI: 10.1111/febs.13987. View

12.

Liu L, Tao Z, Zheng L, Brooke J, Smith C, Liu D . FoxO1 interacts with transcription factor EB and differentially regulates mitochondrial uncoupling proteins via autophagy in adipocytes. Cell Death Discov. 2016; 2:16066. PMC: 5046220. DOI: 10.1038/cddiscovery.2016.66. View

13.

Kang C, Xu Q, Martin T, Li M, Demaria M, Aron L . The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science. 2015; 349(6255):aaa5612. PMC: 4942138. DOI: 10.1126/science.aaa5612. View

14.

Wong P, Puente C, Ganley I, Jiang X . The ULK1 complex: sensing nutrient signals for autophagy activation. Autophagy. 2013; 9(2):124-37. PMC: 3552878. DOI: 10.4161/auto.23323. View

15.

Lei Y, Klionsky D . The Emerging Roles of Autophagy in Human Diseases. Biomedicines. 2021; 9(11). PMC: 8615641. DOI: 10.3390/biomedicines9111651. View

16.

Roczniak-Ferguson A, Petit C, Froehlich F, Qian S, Ky J, Angarola B . The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis. Sci Signal. 2012; 5(228):ra42. PMC: 3437338. DOI: 10.1126/scisignal.2002790. View

17.

Pike L, Singleton D, Buffa F, Abramczyk O, Phadwal K, Li J . Transcriptional up-regulation of ULK1 by ATF4 contributes to cancer cell survival. Biochem J. 2012; 449(2):389-400. DOI: 10.1042/BJ20120972. View

18.

Bartholomew C, Suzuki T, Du Z, Backues S, Jin M, Lynch-Day M . Ume6 transcription factor is part of a signaling cascade that regulates autophagy. Proc Natl Acad Sci U S A. 2012; 109(28):11206-10. PMC: 3396506. DOI: 10.1073/pnas.1200313109. View

19.

Garcia-Garcia A, Rodriguez-Rocha H, Tseng M, Montes de Oca-Luna R, Zhou H, McMasters K . E2F-1 lacking the transcriptional activity domain induces autophagy. Cancer Biol Ther. 2012; 13(11):1091-101. PMC: 3462036. DOI: 10.4161/cbt.21143. View

20.

Yao J, Zheng K, Zhang X . Rosiglitazone exerts neuroprotective effects via the suppression of neuronal autophagy and apoptosis in the cortex following traumatic brain injury. Mol Med Rep. 2015; 12(5):6591-7. PMC: 4626137. DOI: 10.3892/mmr.2015.4292. View