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Review
. 2022 Nov;77(5):1410-1421.
doi: 10.1016/j.jhep.2022.06.019. Epub 2022 Jun 28.

Augmenter of liver regeneration: Mitochondrial function and steatohepatitis

Alok Kumar Verma  1 , Akanksha Sharma  1 , Nithyananthan Subramaniyam  2 , Chandrashekhar R Gandhi  3
Affiliations
Review

Augmenter of liver regeneration: Mitochondrial function and steatohepatitis

Alok Kumar Verma et al. J Hepatol. 2022 Nov.

Abstract

Augmenter of liver regeneration (ALR), a ubiquitous fundamental life protein, is expressed more abundantly in the liver than other organs. Expression of ALR is highest in hepatocytes, which also constitutively secrete it. ALR gene transcription is regulated by NRF2, FOXA2, SP1, HNF4α, EGR-1 and AP1/AP4. ALR's FAD-linked sulfhydryl oxidase activity is essential for protein folding in the mitochondrial intermembrane space. ALR's functions also include cytochrome c reductase and protein Fe/S maturation activities. ALR depletion from hepatocytes leads to increased oxidative stress, impaired ATP synthesis and apoptosis/necrosis. Loss of ALR's functions due to homozygous mutation causes severe mitochondrial defects and congenital progressive multiorgan failure, suggesting that individuals with one functional ALR allele might be susceptible to disorders involving compromised mitochondrial function. Genetic ablation of ALR from hepatocytes induces structural and functional mitochondrial abnormalities, dysregulation of lipid homeostasis and development of steatohepatitis. High-fat diet-fed ALR-deficient mice develop non-alcoholic steatohepatitis (NASH) and fibrosis, while hepatic and serum levels of ALR are lower than normal in human NASH and NASH-cirrhosis. Thus, ALR deficiency may be a critical predisposing factor in the pathogenesis and progression of NASH.

Keywords: Augmenter of liver regeneration; mitochondria; oxidative stress; steatohepatitis; steatosis.

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Conflict of interest statement

Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.

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