Emerging mechanistic insights of selective autophagy in hepatic diseases

Frontiers in Pharmacology

Pharmacology

Alfreda Stadlin¹  Nicholas Peake²  Raouf Fadel³  Nabil Eid⁴  MoezAlIslam Ezzat Faris⁵  Yuko Ito⁶  Paul G. Thomes⁷  Abdul Alim Al-Bari⁸  Marina García-Macia⁹  Manoj B. Menon^1,10  Daniel J. Klionsky^1,11 

[1] Basic Medical Sciences Department, College of Medicine, Ajman university, Ajman, United Arab Emirates;Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, United Kingdom;Department of Anatomy, College of Medicine and Medical Sciences, Arabian Gulf University, Al Manama, Bahrain;Department of Anatomy, Division of Human Biology, School of Medicine, International Medical University, Kuala Lumpur, Malaysia;Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates;Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan;Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States;Department of Pharmacy, Faculty of Science, University of Rajshahi, Rajshahi, Bangladesh;Institute of Functional Biology and Genomics (IBFG), Universidad de Salamanca-CSIC, Institute of Biomedical Research of Salamanca (IBSAL), Hospital Universitario de Salamanca, Salamanca, Spain;Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, India;Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of MI, Ann Arbor, MI, United States;

关键词: autophagy;    lipophagy;    liver disease;    mitophagy;    TFEB;    virophagy;   

DOI  :  10.3389/fphar.2023.1149809

 received in 2023-01-23, accepted in 2023-02-23,  发布年份 2023

来源: Frontiers

【 摘 要 】

Macroautophagy (hereafter referred to as autophagy), a highly conserved metabolic process, regulates cellular homeostasis by degrading dysfunctional cytosolic constituents and invading pathogens via the lysosomal system. In addition, autophagy selectively recycles specific organelles such as damaged mitochondria (via mitophagy), and lipid droplets (LDs; via lipophagy) or eliminates specialized intracellular pathogenic microorganisms such as hepatitis B virus (HBV) and coronaviruses (via virophagy). Selective autophagy, particularly mitophagy, plays a key role in the preservation of healthy liver physiology, and its dysfunction is connected to the pathogenesis of a wide variety of liver diseases. For example, lipophagy has emerged as a defensive mechanism against chronic liver diseases. There is a prominent role for mitophagy and lipophagy in hepatic pathologies including non-alcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC), and drug-induced liver injury. Moreover, these selective autophagy pathways including virophagy are being investigated in the context of viral hepatitis and, more recently, the coronavirus disease 2019 (COVID-19)-associated hepatic pathologies. The interplay between diverse types of selective autophagy and its impact on liver diseases is briefly addressed. Thus, modulating selective autophagy (e.g., mitophagy) would seem to be effective in improving liver diseases. Considering the prominence of selective autophagy in liver physiology, this review summarizes the current understanding of the molecular mechanisms and functions of selective autophagy (mainly mitophagy and lipophagy) in liver physiology and pathophysiology. This may help in finding therapeutic interventions targeting hepatic diseases via manipulation of selective autophagy.

【 授权许可】

Unknown   
Copyright © 2023 Alim Al-Bari, Ito, Thomes, Menon, García-Macia, Fadel, Stadlin, Peake, Faris, Eid and Klionsky.