The cell biologist Yoshinori Ohsumi received the 2016 Nobel Prize in Medicine for his early identification and characterization of the autophagy machinery, in particular, AuTophaGy-related (Atg) genes, in yeast. Macroautophagy (hereafter, autophagy) is a cytoprotective pathway for sequestration of cellular components (such as misfolded proteins, damaged organelles, and excessive lipids) into autophagosomal vesicles, followed by clearance via the lysosomal system (Galluzzi et al., 2017). Autophagy is specifically upregulated upon exposure to various stressors such as oxidative and endoplasmic reticulum stress, thus aiding in the prevention of various pathologies. Therefore, autophagy dysregulation may be involved in inflammatory, metabolic, toxic, and infectious diseases and cancer (Kroemer et al., 2010; Eid et al., 2013; Horibe et al., 2017). Most organelles also seem to have selective programs of autophagy, including mitochondria, lipid droplets, endoplasmic reticulum, and even lysosomes. Selective autophagic removal of damaged mitochondria, or mitophagy, is an anti-apoptotic mechanism induced and specifically upregulated in response to various damaging agents such as binge ethanol exposure or drug-induced liver injury in animal models (Otsuki et al., 1994; Youle and Narendra, 2011; Lemasters, 2014; Eid et al., 2016; Eid et al., 2019). Autophagy can be regulated not only at the gene level, but its final performance can be modulated by lysosomal lipid composition. For instance, accumulation of lipids (e.g., cholesterol) in lysosomes has been shown to impair the fusion of autophagosomes (containing disrupted mitochondria) with lysosomes, contributing to the perpetuation of damaged mitochondria, which sensitizes to acetaminophen hepatotoxicity (Baulies et al., 2015). On the other hand, autophagic clearance of lipid droplets is referred to as lipophagy (Singh and Cuervo, 2012). Various transcription factors such as transcription factor EB (TFEB), Nrf2, HIF, and Foxo3a play important roles in the regulation of autophagy and mitophagy-related proteins such as LC3, cathepsins, and Parkin (Sardiello, 2016; Horibe et al., 2017; Eid et al., 2019). The focus of this Research Topic is to highlight the involvement of these transcription factors in the regulation of liver and gut diseases through autophagy pathway as these are potential therapeutic targets for the restoration of autophagy and in the management of these diseases.
ASJC Scopus subject areas
- Pharmacology (medical)