Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 154, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2021.112351
Keywords
Cardiolipin; Cytochrome c release; Lipotoxicity; Metabolic disease; Mitochondria; Palmitoyl-CoA
Categories
Funding
- CONACYT [583627]
- Instituto Nacional de Cardiologia
- CONACYT, Mexico [106845]
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The release of cytochrome c from liver mitochondria into the cytosol is a key process in hepatocyte apoptosis involved in the progression of non-alcoholic fatty liver disease (NAFLD) to more severe conditions. The study found that palmitoyl-CoA-induced cytochrome c release is sensitive to cyclosporine A, indicating the involvement of mitochondrial membrane permeability transition (mMPT). Despite increased H2O2 generation, cytochrome c release from sucrose-fed (SF) rat mitochondria remains significantly lower than normal mitochondria, possibly due to the enrichment of cardiolipin molecular species with palmitic acid.
Cytochrome c (cyt-c) release from the mitochondria to the cytosol is a key process in the initiation of hepatocyte apoptosis involved in the progression of non-alcoholic fatty liver disease (NAFLD) to fibrosis, cirrhosis and hepatocellular carcinoma. Hepatocyte apoptosis may be related to lipotoxicity due to the accumulation of palmitic acid and palmitoyl-CoA (Pal-CoA). Therefore, the aim of this study is to examine whether Pal-CoA induces cyt-c release from liver mitochondria of sucrose-fed rat (SF). Pal-CoA-induced cyt-c release was sensitive to cyclosporine A indicating the involvement of the mitochondrial membrane permeability transition (mMPT). In addition, cyt-c release from SF mitochondria remains significantly lower than C mitochondria despite the increased rate of H2O2 generation in SF mitochondria. The decreased cyt-c release from SF may be also related to the increased proportion of the palmitic acid-enriched cardiolipin, due to the high availibilty of palmitic acid in SF liver. The enrichment of cardiolipin molecular species with palmitic acid makes cardiolipin more resistant to peroxidation, a mechanism involved in the dissociation of cyt-c from mitochondrial inner membrane. These results suggest that Pal-CoA may participate in the progression of NAFLD to more severe disease through mechanisms involving cyt-c release and mMPT, a key process of apoptosis.
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