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

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

• Yi HS

• KMID: 2441677
• DOI: http://doi.org/10.3803/EnM.2019.34.1.39

Abstract

The signaling network of the mitochondrial unfolded protein response (UPR(mt)) and mitohormesis is a retrograde signaling pathway through which mitochondria-to-nucleus communication occurs in organisms. Recently, it has been shown that the UPR(mt) 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 UPR(mt) 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 UPR(mt) and mitohormesis in metabolic liver diseases, including NAFLD/NASH and fibrosis.

Keyword

Mitochondria; Fatty liver; Metabolism; Obesity; Insulin resistance

MeSH Terms

Alcoholics
Fatty Liver*
Fibrosis
Humans
Insulin Resistance
Liver Diseases
Metabolism
Mitochondria
Non-alcoholic Fatty Liver Disease
Obesity
Proteome
Quality Control
Unfolded Protein Response*
Proteome

Figure

• 

  Fig. 1 Scheme depicting the mitochondrial unfolded protein response (UPRmt) and mitokines. As a cell autonomous response, damaged mitochondria within a cell communicate to the nucleus via retrograde signaling. In contrast, mitokines (as a cell non-autonomous factor) are induced during the UPRmt and are secreted from cells affected by mitochondrial stress. OXPHOS, oxidative phosphorylation; FGF21, fibroblast growth factor 21; GDF15, growth differentiation factor 15; Hspd1, heat shock protein family D member 1; ClpP, caseinolytic peptidase P; Lonp1, LON protease 1.

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