Mitochondria and the NLRP3 Inflammasome in Alcoholic and Nonalcoholic Steatohepatitis.

Abstract

Alcoholic (ASH) and nonalcoholic steatohepatitis (NASH) are advanced stages of fatty liver disease and two of the most prevalent forms of chronic liver disease. ASH and NASH are associated with significant risk of further progression to cirrhosis and hepatocellular carcinoma (HCC), the most common type of liver cancer, and a major cause of cancer-related mortality. Despite extensive research and progress in the last decades to elucidate the mechanisms of the development of ASH and NASH, the pathogenesis of both diseases is still poorly understood. Mitochondrial damage and activation of inflammasome complexes have a role in inducing and sustaining liver damage. Mitochondrial dysfunction produces inflammatory factors that activate the inflammasome complexes. NLRP3 inflammasome (nucleotide-binding oligomerization domain-like receptor protein 3) is a multiprotein complex that activates caspase 1 and the release of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and interleukin-18 (IL-18), and contributes to inflammatory pyroptotic cell death. The present review, which is part of the issue “Mitochondria in Liver Pathobiology”, provides an overview of the role of mitochondrial dysfunction and NLRP3 activation in ASH and NASH.