Implications of Mitochondrial Unfolded Protein Response and Mitokines: A Perspective on Fatty Liver Diseases

Endocrinol Metab (Seoul). 2019 Mar;34(1):39-46. doi: 10.3803/EnM.2019.34.1.39.

Abstract

The signaling network of the mitochondrial unfolded protein response (UPRmt) and mitohormesis is a retrograde signaling pathway through which mitochondria-to-nucleus communication occurs in organisms. Recently, it has been shown that the UPRmt is closely associated with metabolic disorders and conditions involving insulin resistance, such as alcoholic and non-alcoholic fatty liver and fibrotic liver disease. Scientific efforts to understand the UPRmt and mitohormesis, as well as to establish the mitochondrial proteome, have established the importance of mitochondrial quality control in the development and progression of metabolic liver diseases, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In this review, we integrate and discuss the recent data from the literature on the UPRmt and mitohormesis in metabolic liver diseases, including NAFLD/NASH and fibrosis.

Keywords: Fatty liver; Insulin resistance; Metabolism; Mitochondria; Obesity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Activating Transcription Factor 4 / metabolism
  • Animals
  • Diet, High-Fat / adverse effects
  • Diet, High-Fat / methods
  • Disease Progression
  • Fibroblast Growth Factors / metabolism
  • Fibrosis / metabolism
  • Humans
  • Insulin Resistance / physiology
  • Liver Diseases / metabolism
  • Liver Diseases / pathology
  • Metabolic Diseases / metabolism
  • Mice
  • Mitochondria / metabolism*
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Obesity / complications
  • Obesity / drug therapy
  • Proteome / metabolism
  • Rats
  • Signal Transduction / genetics*
  • Unfolded Protein Response / physiology*

Substances

  • Proteome
  • fibroblast growth factor 21
  • Activating Transcription Factor 4
  • Fibroblast Growth Factors