Autophagy and Related Transcription Factors in Liver and Gut Diseases

Macroautophagy (hereafter, autophagy) is essentially a prosurvival pathway for the clearance of almost all cellular components, such as damaged organelles, excessive lipids and abnormal proteins. It could be selective for specific organelles such as mitochondria (mitophagy) or lipid droplets (lipophagy) or even invading pathogens (xenophagy). A growing body of evidence indicates that autophagy may regulate various liver and gut diseases, including inflammatory, metabolic, toxic, infectious and neoplastic pathologies. For instance, upregulation of mitophagy and lipophagy are cytoprotective for hepatocytes in vitro and in animal models of alcoholic and non-alcoholic liver diseases. On the contrary, suppression of autophagy was found to stimulate inflammatory bowel disease (IBD). Interestingly, autophagy acts as a tumor suppressor mechanism in early phases of cancer; but it ends up protecting cancer cells in the later phases of malignancy. Autophagy-related genes such as LC3 are positively regulated by various transcription factors such as TFEB, Nrf2, HIF and Foxo3a. However, the specific roles of these transcription factors in liver and gut diseases, including malignancies, and the signaling mechanisms which may regulate their relationship with selective or non-selective autophagy are not clearly understood. Understanding the specific roles of these transcription factors in regulating autophagy in the liver and gut diseases may help to develop specific therapeutic options using pharmacological or natural products.

The focus of this Frontiers Research Topic includes, but is not limited to, autophagy and related transcription factors and their role in liver and gut diseases. In vitro and animal models of these diseases (inflammatory, metabolic, neoplastic, infectious, toxic) and studies investigating pharmacological modulation of autophagy and related transcription factors in these diseases are welcome. We intend to generate a compendium of articles including original research and thought-provoking reviews, on the interplay of transcriptional networks regulating autophagy in the context of these organ systems.