Mercury-induced dysfunctions in multiple organelles leading to cell death

Mercury (Hg) is a highly toxic metal that can exert multiple adverse effects, ultimately leading to cell death. Before causing death, the Hg enters the cells and affects diverse intracellular targets. The present study aimed to investigate the structure and function of several organelles or cellular structures, including mitochondria, acidic compartments and vesicles, endoplasmic reticulum elements and microfilaments, following Hg exposure of a human hepatic cell line (HuH-7 cells) to examine the sequence and coordination of the events associated with Hg-induced cell death. Hg exposure led to a progressive decrease in cell viability and induced alterations in cell morphology including cytoplasmic shrinkage and nuclear fragmentation. Hg treatment (10 mu M for 12 h) affected multiple intracellular targets simultaneously. These included loss of mitochondrial functionality, pronounced cytoplasmic acidification and dysfunctions in the cytoskeleton and endoplasmic reticulum. This overall Hg-induced toxicity in the human hepatocyte cell line (HuH-7 cells) led to cell death through both apoptosis and autophagy. (C) 2014 Elsevier Ltd. All rights reserved.