Whole mitochondria genome mutational spectrum in occupationally exposed lead subjects

Publication date: Available online 25 April 2019Source: MitochondrionAuthor(s): Monica Shirley Mani, Sanjiban Chakrabarty, Sandeep P. Mallya, Shama Prasada Kabekkodu, Pradyumna Jayaram, Vinay Koshy Varghese, Herman Sunil Dsouza, Kapaettu SatyamoorthyAbstractLead is a public health hazard substance affecting millions of people worldwide especially those who are occupationally exposed. Our study aimed to investigate the effect of occupational lead exposure on mitochondria DNA (mtDNA). By sequencing the whole mitochondria genome, we identified 25 unique variants in lead exposed subjects affecting 10 protein coding genes in the order of MT-ND1, MT-ND2, MT-CO2, MT-ATP8, MT-ATP6, MT-CO3, MT-ND3, MT-ND4, MT-ND5, and MT-CYB. Mitochondria functional analysis revealed that exposure to lead can reduce reactive oxygen species (ROS) levels, alter mitochondria membrane potential (MMP) and increase mitochondrial mass (MM). This was further supported by mtDNA copy number analysis which was increased in lead exposed individuals compared to unexposed control group indicating the compensatory mechanism that lead has in stabilizing the mitochondria. This is the first report of mtDNA mutation and copy number analysis in occupationally lead exposed subjects where we identified mtDNA mutation signature associated with lead exposure thus providing evidence for altered molecular mechanism to compensate mitochondrial oxidative stress.
Source: Mitochondrion - Category: Biochemistry Source Type: research