Whole mitochondria genome mutational spectrum in occupationally exposed lead subjects

Lead 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 v...

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Bibliographic Details
Published in:Mitochondrion 2019-09, Vol.48, p.60-66
Main Authors: Mani, Monica Shirley, Chakrabarty, Sanjiban, Mallya, Sandeep P, Kabekkodu, Shama Prasada, Jayaram, Pradyumna, Varghese, Vinay Koshy, Dsouza, Herman Sunil, Satyamoorthy, Kapaettu
Format: Article
Language:English
Subjects:
Adult
DNA, Mitochondrial - genetics
Genes, Mitochondrial - drug effects
Genes, Mitochondrial - genetics
Genome, Mitochondrial - drug effects
Genome, Mitochondrial - genetics
Humans
Lead - adverse effects
Male
Membrane Potential, Mitochondrial - drug effects
Membrane Potential, Mitochondrial - genetics
Mitochondria - drug effects
Mitochondria - genetics
Mutation - drug effects
Mutation - genetics
Oxidative Stress - drug effects
Oxidative Stress - genetics
Reactive Oxygen Species - metabolism
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Summary:Lead 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.
ISSN:1567-7249
1872-8278
DOI:10.1016/j.mito.2019.04.009