Clinical effects of chemical exposures on mitochondrial function

Abstract

Mitochondria are critical for the provision of ATP for cellular energy requirements. Tissue and organ functions are dependent on adequate ATP production, especially when energy demand is high. Mitochondria also play a role in a vast array of important biochemical pathways including apoptosis, generation and detoxification of reactive oxygen species, intracellular calcium regulation, steroid hormone and heme synthesis, and lipid metabolism. The complexity of mitochondrial structure and function facilitates its diverse roles but also enhances its vulnerability. Primary disorders of mitochondrial bioenergetics, or Primary Mitochondrial Diseases (PMD) are due to inherited genetic defects in the nuclear or mitochondrial genomes that result in defective oxidative phosphorylation capacity and cellular energy production. Secondary mitochondrial dysfunction is observed in a wide range of diseases such as Alzheimer’s and Parkinson’s disease. Several lines of evidence suggest that environmental exposures cause substantial mitochondrial dysfunction. Whereby literature from experimental and human studies on exposures associated with Alzheimer’s and Parkinson’s diseases exist, the significance of exposures as potential triggers in Primary Mitochondrial Disease (PMD) is an emerging clinical question that has not been systematically studied.

Susceptibility to COVID‐19 in populations with health disparities: Posited involvement of mitochondrial disorder, socioeconomic stress, and pollutants

“…[ 10,11 ] Children of white and non‐Hispanic ancestry with a higher median income have been reported to have a higher prevalence of MtD [ 12 ] ; however, the phenotypes and genetic abnormalities of MtD have been increasing since earlier investigations in 1988, [ 13 ] which has raised the question of environmental influences. [ 14 ]…”

The antiretroviral 2′,3′-dideoxycytidine causes mitochondrial dysfunction in proliferating and differentiated HepaRG human cell cultures

“…We expect that the long-term exposure to mtDNA toxicants will be harmful to both proliferating and nonproliferating cell mitochondria in vivo . Awareness about the toxic effect of drugs and pollutants on mitochondrial function is rapidly accelerating ( 19 , 68 , 69 , 70 ). For example, hepatitis C virus ribonucleoside analogs designed to inhibit viral RNA synthesis have been demonstrated to have off-target effects on the human mitochondrial RNA polymerase, POLRMT ( 71 ).…”

A versatile EPR toolbox for the simultaneous measurement of oxygen consumption and superoxide production

“…Regarding experiments on isolated mitochondria, the substrates used can be adapted depending on the type of state respiration studied. The method seems particularly suitable to screen the effect of compounds altering the mitochondrial function, for example toxic substances inducing mitochondrial dysfunction [ [37] , [38] , [39] ], new mitochondrial targeted anti-cancer agents [ 35 , 40 , 41 ] or modulators of metastatic progression through mitochondrial superoxide scavenging [ 11 , 42 ].…”