Role of MST1 in the regulation of autophagy and mitophagy: implications for aging-related diseases
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Shang, Huayu [1] ; VanDusseldorp, Trisha A. [2] ; Ma, Ranggui [1] ; Zhao, Yan [3] ; Cholewa, Jason [5] ; Zanchi, Nelo Eidy [4] ; Xia, Zhi [3]
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[1] Chengdu Sport University
Chengdu Sport University
China
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[2] Kennesaw State University
Kennesaw State University
Estados Unidos
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[3] Wenzhou University
Wenzhou University
China
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[4] Universidade Federal do Maranhão
Universidade Federal do Maranhão
Brasil
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[5] Department of Exercise Physiology, University of Lynchburg, Lynchburg, VA, USA
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- Localización: Journal of physiology and biochemistry, ISSN-e 1877-8755, ISSN 1138-7548, Vol. 78, Nº. 4, 2022, págs. 709-719
- Idioma: inglés
- Enlaces
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Resumen
As a key mechanism to maintain cellular homeostasis under stress conditions, autophagy/mitophagy is related to the occurrence of metabolic disorders, neurodegenerative diseases, cancer, and other aging-related diseases, but the relevant signal pathways regulating autophagy have not been clarified. Mammalian sterile 20-like kinase 1 (MST1) is a central regulatory protein of many metabolic pathways involved in the pathophysiological processes of aging and aging-related diseases and has become a critical integrator affecting autophagic signaling. Recent studies show that MST1 not only suppresses autophagy through directly phosphorylating Beclin-1 and/or inhibiting the protein expression of silent information regulator 1 (SIRT1) in the cytoplasm, but also inhibits BCL2/adenovirus E1B protein-interacting protein 3 (BNIP3)–, FUN14 domain containing 1 (FUNDC1)–, and Parkin (Parkinson protein 2)–mediated mitophagy by interacting with factors such as Ras association domain family 1A (RASSF1A). Indeed, a common pharmacological strategy for anti-aging is to induce autophagy/mitophagy through MST1 inhibition. This article reviews the role and mechanism of MST1 in regulating autophagy during aging, to provide evidence for the development of drugs targeting MST1.
