Role of MST1 in the regulation of autophagy and mitophagy: implications for aging-related diseases

Department

Exercise Science and Sport Management

Document Type

Article

Publication Date

6-21-2022

Abstract

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.

Journal Title

Journal of Physiology and Biochemistry

Journal ISSN

11387548

Digital Object Identifier (DOI)

10.1007/s13105-022-00904-6

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