Dynamin-1-like protein inhibition drives megamitochondria formation as an adaptive response in alcohol-induced hepatotoxicity.

In this study, we investigated the mitochondrial and cellular response to alcohol in hepatoma cell line VL-17A. The mitochondrial architecture rapidly changed after 3 or 14 days of ethanol exposure with double-pronged presentation of hyper-fragmentation and megamitochondria and cell growth was inhibited. Dynamin-1-like protein (Drp1) was identified as the main mediator driving these mitochondrial alterations and its genetic inactivation was determined to foster megamitochondria development, preserving the capacity of the cells to grow despite alcohol toxicity. The role of Drp1 in mediating megamitochondria formation in mice with liver-specific inactivation of Drp1 was further confirmed. Finally, when these mice were fed with ethanol, the presentation of hepatic megamitochondria was exacerbated compared to wild type fed with the same diet. Ethanol-induced toxicity was also reduced. Our study demonstrates that megamitochondria formation is mediated by Drp1 and this phenomenon is a beneficial adaptive response during alcohol-induced hepatotoxicity. PMID: 30553835 [PubMed - as supplied by publisher]
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research