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Molecular insights into the role of mitochondria in non-alcoholic fatty liver disease

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Abstract

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of fatal liver diseases such as cirrhosis, liver cancer, and indications for orthotopic liver transplantation. Given its high prevalence, the absence of FDA-approved drugs for NAFLD is noticeable. In the pathogenesis of NAFLD, it is well known that mitochondrial dysfunction arises as a result of changes in ETC complexes and the membrane potential (Δψm), as well as decreased ATP synthesis. Due to their fundamental role in energy metabolism and cell death decision, alterations in mitochondria are considered to be critical factors causing NAFLD. Reduced levels of β-oxidation, along with increased lipogenesis, result in lipid accumulation in hepatocytes, and the subsequent production of reactive oxygen species and hepatocyte injury, which contribute to hepatic inflammation and fibrosis through the activations of Kupffer cells and hepatic stellate cells. Here, we review the latest findings describing the involvement of mitochondrial processes in the development of NAFLD and discuss the potential targets against which therapeutics for this disease can be developed.

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) Grant by the Korea government (MEST; MRC, 2017R1A5A2015541, NRF-2017R1C1B2004423 and 2019R1A2C1090178).

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  1. Jin Lee and Jeong-Su Park contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA

    Jin Lee

  2. Department of Pharmacy, College of Pharmacy and Medical Research Center, Chungbuk National University, 194-21 Osongsaengmyung-1 Ro, Cheongju, Chungbuk, 28160, South Korea

    Jeong-Su Park & Yoon Seok Roh

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  1. Jin Lee
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  2. Jeong-Su Park
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  3. Yoon Seok Roh
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Correspondence to Yoon Seok Roh.

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Lee, J., Park, JS. & Roh, Y.S. Molecular insights into the role of mitochondria in non-alcoholic fatty liver disease. Arch. Pharm. Res. 42, 935–946 (2019). https://doi.org/10.1007/s12272-019-01178-1

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  • DOI: https://doi.org/10.1007/s12272-019-01178-1

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