Table 2.

Environmental toxicants and their respective mitochondrial dysfunction measured in animal and in vitro studies outlined in this review. Biospecimen column refers to the tissue the mitochondrial biomarker was measured in

Compound	Species	Biospecimen	Dose/duration	Result	Citation
PAHS
Benzo[a]pyrene	Human	Blood lymphocytes	10 µM for 1, 3, 6, 12, 24, 48, or 72 h	Altered expression of mitochondrial targeting microRNAs and epigenetic modifiers, and hypomethylation of mtDNA	Bhargava et al. 2020 [78]
	Human	Tk6 cells	0.05, 0.5, 5.0, 50, 500 µM for 24 h	↓ Copy number	Pieters et al. 2013 [88]
Heavy metals
Cadmium	Human	Osteoblasts	65 μM for 24 or 48 h	↑ Oxidative stress, ↓ antioxidant gene expression, and ↓ MMP	Monteiro et al. 2018 [122]
	Human	PC12 cells	10, 50, 100, 500 µM for 3 or 24 h	Uncoupled cellular respiration	Belyaeva et al. 2012 [111]
	Guinea pig	Isolated heart, brain, liver mitochondria	0, 10, 20, 30, 40, 50 µM for 10 min	↑ ROS production and ↓ activity of complexes II and III	Wang et al. 2004 [121]
	Rat	Isolated liver mitochondria	1–100 µM for 1 min/stage	↑ Mitochondrial swelling	Belyaeva et al. 2002 [133]
	Rat	Isolated liver mitochondria	0–30 µM for 30 min	↑ Mitochondrial swelling, ↓ respiration, ↓ MMP, and ↓ preaccumulated Ca2+	Al-Nasser 2000 [135]
Aluminum	Human	PC12 cells	125–2000 µM for 48 h	↑ ROS and apoptosis, ↓ MMP, and catalase activity	Iranpak et al. 2019 [129]
Mercury	Human	PC12 cells	10, 50, 100, 500 µM for 3 or 24 h	Uncoupled cellular respiration	Belyaeva et al. 2012 [111]
Copper	Human	GC-1 cell line	0, 10, 50, 100 µM for 24 h	↓ MMP, ATP levels, and mitochondrial fission	Kang et al. 2019 [124]
	Rat	Isolated brain, liver, kidneys, heart mitochondria	500 and 1340 µM for 48 h	↓ MMP and ATP production, and altered mitochondrial structure	Borchard et al. 2018 [131]
	Rat	Isolated hippocampus mitochondria	50, 100, 200 mg/kg/day for 21 days	↑ ROS, ↑ mitochondrial swelling, ↑ lipid peroxidation, ↑ glutathione oxidation, ↑ outer membrane damage, ↓ MMP, ↓ cytochrome c oxidase activity, and ↑ ADP/ATP ratios	Behzadfar et al. 2017 [132]
	Human	PC12 cells	10, 50, 100, 500 µM for 3 or 24 h	Uncoupled cellular respiration	Belyaeva et al. 2012 [111]
Lead	Rat	Brain	220 ppm for 25 days	↑ Catalase activity and ↓ ALDH2 expression	Mattalloni et al. 2019 [126]
	Rat	Isolated brain mitochondria	0.2% in H2O for 37 days	↓ Enzyme activity and ↑ MDA levels	Gottipolu and Davuljigari 2014 [125]
	Yeast		0, 100, 250, 500, 1000 µM for 3 h	↑ ROS and ↑ mtDNA mutations	Sousa and Soares, 2014 [136]
Arsenic	Rat	Hippocampus	20 mg/kg for 21 days	↑ ROS, ↓ MMP, mitochondrial swelling, and release of cytochrome c	Keshavarz-Bahaghighat et al. 2018 [128]
Endocrine-disrupting compounds
Di(2-ethylhexyl) phthalate	Quail	Liver	0, 250, 500, 1000 mg/kg/day for 45 days	↑ MDA, ↑ GSH and GST levels, ↓ antioxidant function, and ↑ mitochondrial structural abnormalities	Zhang et al. 2019 [141]
Bisphenol A	C. elegans		500 µM for 24 h	↑ Oxidative stress and mitochondrial dysfunction	Hornos Carneiro et al. 2020 [142]
	Rat	Liver	50 or 500 µg/kg/day for 20 wks	Dysregulated expression of ETC genes and altered expression of antioxidant genes	Azevedo et al. 2020 [151]
	Rat	Isolated liver mitochondria	40 µg/kg/day for ~ 42 days	↓ Complex I and III activity, ↓ ATP production, ↑ ROS, and cytochrome c release	Jiang et al. 2014 [149]
	Human	Lymphoblasts	0, 25, 50, 100 µM for ~ 12 h	↑ ROS, ↓ MMP, and ↑ copy number	Kaur et al. 2014 [146]
Nonylphenol	Rat	Pancreas	0, 20, 60, 180 mg/kg for 90 days	↑ ROS, ↓ MMP, and ↑ intracellular Ca2+	Li et al. 2017 [144]
Mono-2-ethylhexyl phthalate	Mouse	Leydig cells	1, 3, 10, 30, 90 µM for 48 h	↓ ATP production and ↑ ROS	Savchuk et al. 2015 [143]
Pesticides
Mixed organochlorine pesticides	L6 myotube and zebra fish		Myotube: 0.5, 50, 5000 nmol for 48 h; zebra fish 0.15 and 75 nmol/L for 48 h	↑ ROS and ↓ mitochondrial quantity	Park et al. 2021 [155]
Dichloro diphenyl dichloroethylene	Mouse	Hepatocytes	DDE 1 mg/kg/day or HCH 10 mg/kg/day for 8 days	Changes in TCA metabolites, ↓ MMP, ↓ ATP levels, and ↓ oxygen consumption rate	Liu et al. 2017 [156]
Atrazine	C. elegans		0, 0.001, 0.01, 0.1, 1, 10 ng/L ~ 4.5 days	↑ ROS and activated mitochondrial unfolded protein response	Zhou et al. 2021 [164]
	Pig	Oocyte	0, 50, 100, 200, 500 µM for ~ 43 h	↑ ROS, ↓ MMP, and ↓ GSH production	Yuan et al. 2017 [160]
Paraquat	Human	Brain microvascular endothelial cells	1, 10, 100 μM for 24 h	↓ Complex I proteins	Tatjana et al. 2021 [162]
	Mouse	Cardiomyocytes	45 mg/kg for 48 h	↓ MMP	Wang et al. 2014 [164]
	Rat	Isolated brain mitochondria	30, 100, 300 µM for 10 min	↑ ROS	Drechsel et al. 2009 [161]
Nanoparticles
Silver nanoparticles	Rat	Isolated liver mitochondria	40 or 80 nM for 10 min	↓ MMP, ↓ in ADP-induced depolarization, and ↓ respiratory control ratio	Teodoro et al. 2011 [168]
Cadmium telluride quantum dots	Human	Bronchial epithelial cells	20 µg/mL for 24 h	↑ Oxidative stress	Xu et al. 2019 [170]
	Human	Hepatocellular carcinoma HepG2 cells	10 mg/mL for 1 h	Enlarged mitochondria, disrupted ΔΨm, ↑ intracellular Ca2+, ↓ ATP, and ↑ mitochondrial biogenesis
Pristine graphene	Human	U87 and HS-5 cells	0, 20, 50, 100, 200 µg/mL for 24 h	↑ ROS and ↓ MMP	Jaworski et al. 2019 [172]
Titanium dioxide nanoparticles	Human	HeLa cells	270 or 500 µg/mL for 1 h	↑ ROS	Jayaram et al. 2017 [173]
Hydroxyapatite	Rat	Hepatocytes	200–800 µg/mL for 24 h	↓ MMP, ↑ ROS, ↑ MDA, ↓ GSH, and ↓ complex I, II, and III activity	Xue et al. 2017 [174]
	Rat	Liver	50 mg/kg for 48 h	Mitochondrial swelling and ↓ succinate
Graphene oxide	Zebra fish	Brain	0.01 and 0.1 µg/L for 24 h	↑ Oxidative stress and mitochondrial structural abnormalities	Ren et al., 2016 [176]

mtDNA mitochondrial DNA, MMP mitochondrial membrane potential, ROS reactive oxygen species, ATP adenosine triphosphate, ADP adenosine diphosphate, ALDH2 aldehyde dehydrogenase, MDA malondialdehyde, GSH glutathione, GST glutathione s-transferase, ETC electron transport chain, TCA tricarboxylic acid cycle