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Epigenetic regulation of autophagy by histone-modifying enzymes under nutrient stress

Cell Death & Differentiation volume 30, pages 1430–1436 (2023)Cite this article

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Abstract

Autophagy is an evolutionarily conserved catabolic process that is induced in response to various stress factors in order to protect cells and maintain cellular homeostasis by degrading redundant components and dysfunctional organelles. Dysregulation of autophagy has been implicated in several conditions such as cancer, neurodegenerative diseases, and metabolic disorders. Although autophagy has been commonly considered as a cytoplasmic process, accumulating evidence has revealed that epigenetic regulation within the nucleus is also important for regulation of autophagy. In particular, when energy homeostasis is disrupted, for instance due to nutrient deprivation, cells increase autophagic activity at the transcriptional level, thereby also increasing the extent of overall autophagic flux. The transcription of genes associated with autophagy is strictly regulated by epigenetic factors through a network of histone-modifying enzymes along with histone modifications. A better understanding of the complex regulatory mechanisms of autophagy could reveal potential new therapeutic targets for autophagy-related diseases. In this review, we discuss the epigenetic regulation of autophagy in response to nutrient stress, focusing on histone-modifying enzymes and histone modifications.

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Fig. 1: Autophagy gene regulation via histone acetylation.
Fig. 2: Regulation of autophagy-associated genes via histone methylation.
Fig. 3: Chromatin remodeling in nutrient-deficient condition promotes cell survival by inducing autophagy.

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Acknowledgements

Figures in this review were created using BioRender.com. Creative Research Initiatives Program (Research Center for Epigenetic Code and Diseases) [2017R1A3B1023387 to SHB]; Science Research Center Program (Cellular Heterogeneity Research Center) [NRF-RS-2023-00207857 to KIK]; Basic Science Research Program [NRF-2021R1A2C1006680 to KIK]; Basic Science Research Program [NRF-2022R1A2C2010940 to HK]; Sejong Science Fellowship Program [NRF-2021R1C1C2010332 to YSY] from the National Research Foundation (NRF) grant funded by the Korea government.

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Authors and Affiliations

  1. Creative Research Initiatives Center for Epigenetic Code and Diseases, Department of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea

    Young Suk Yu & Sung Hee Baek

  2. Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 02841, Republic of Korea

    Hyunkyung Kim

  3. BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, 02841, Republic of Korea

    Hyunkyung Kim

  4. Department of Biological Sciences, Sookmyung Women’s University, Seoul, 04310, Republic of Korea

    Keun Il Kim

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  1. Young Suk Yu
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YSY, HK, KIK, and SHB wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Hyunkyung Kim, Keun Il Kim or Sung Hee Baek.

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Yu, Y.S., Kim, H., Kim, K.I. et al. Epigenetic regulation of autophagy by histone-modifying enzymes under nutrient stress. Cell Death Differ 30, 1430–1436 (2023). https://doi.org/10.1038/s41418-023-01154-9

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