Lead and mercury are the ubiquitous heavy metals triggering toxicity and initiating apoptosis in cells. Though the toxic effects of heavy metals on various organs are known, there is a paucity of information on the mechanisms that instigate the current study. A plausible role of phospholipid scramblase 3 (PLSCR3) in Pb2+ and Hg2+ induced apoptosis was investigated with human embryonic kidney (HEK 293) cells. After 12 h of exposure, ~30-40% of the cells were in the early stage of apoptosis with increased reactive oxygen species (ROS), decreased mitochondrial membrane potential, and increased intracellular calcium levels. Also, ~20% of the cardiolipin localized within the inner mitochondrial membrane was translocated to the outer mitochondrial membrane along with the mobilization of truncated Bid (t-Bid) to the mitochondria and cytochrome c from the mitochondria. The endogenous expression levels of PLSCR3, caspase 8, and caspase 3 were upregulated in Pb2+ and Hg2+ induced apoptosis. The activation and upregulation of PLSCR3 mediate CL translocation playing a potential role in initiating the heavy metal-induced apoptosis. Therefore, PLSCR3 could be the linker between mitochondria and heavy metal apoptosis.
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