Paraquat exposure over generation affects lifespan and reproduction through mitochondrial disruption in C. elegans.
Toxicology. 2021 01 15 ;447:152632. Epub 2020 Nov 13. PMID: 33197508
Paraquat (methyl viologen), is a non-selective contact herbicide and well known mitochondrial toxicant. Mitochondria are the center of cellular metabolism, and involved in the development, lifespan, and reproduction of an organism. Mitochondria are dynamic organelles that are inherited maternally through the germline and carry multiple copies of their own genome (mtDNA). It is important to understand the effects of acute and chronic stress caused by mitochondrial toxicants over multiple generations at the cellular and organism levels. Using the model nematode C. elegans, we show that acute and chronic exposure to paraquat affects reproduction, longevity, gene expression, and mitochondrial physiology. Acute exposure to paraquat in N2 (wild type) causes induction of mitochondrial unfolded protein response (mtUPR), increased expression of mitochondrial superoxide dismutase, decreased mitochondrial membrane potential (Δψm), a dose-dependent progression from linear to fragmented mitochondria, and dose-dependent changes in longevity. Chronic exposure to a low dose of paraquat (0.035 mM) over multiple generations in N2 causes a progressive decline of fertility, leading to complete loss of fertile embryo productionby the third generation. The mutation in CEP-1 [cep-1(gk138)], a key regulator of stress-induced apoptosis in the germline, causes increased sensitivity to chronic paraquat relative to N2 with no fertile embryo production beyond the second generation. Whereas, mitochondrial electron transport chain(complex III) mutant [isp-1(qm150)], which display constitutive activation of mtUPR showed increased tolerance and produced fertile embryo out to the fourth generation. The N2, cep-1(gk138), and isp-1(qm150) strain's lifespan over multiple generations exposed to chronic paraquat were measured. Fertility and lifespan data together indicate a trade-off between reproduction and somatic maintenance during chronic paraquat exposure. We have proposed that mitochondrial signaling, dynamics, and CEP-1 mediated germline apoptosis is involved in this trade-off.