| RRC ID |
75969
|
| 著者 |
Hershberger KA, Rooney JP, Turner EA, Donoghue LJ, Bodhicharla R, Maurer LL, Ryde IT, Kim JJ, Joglekar R, Hibshman JD, Smith LL, Bhatt DP, Ilkayeva OR, Hirschey MD, Meyer JN.
|
| タイトル |
Early-life mitochondrial DNA damage results in lifelong deficits in energy production mediated by redox signaling in Caenorhabditis elegans.
|
| ジャーナル |
Redox Biol
|
| Abstract |
The consequences of damage to the mitochondrial genome (mtDNA) are poorly understood, although mtDNA is more susceptible to damage resulting from some genotoxicants than nuclear DNA (nucDNA), and many environmental toxicants target the mitochondria. Reports from the toxicological literature suggest that exposure to early-life mitochondrial damage could lead to deleterious consequences later in life (the "Developmental Origins of Health and Disease" paradigm), but reports from other fields often report beneficial ("mitohormetic") responses to such damage. Here, we tested the effects of low (causing no change in lifespan) levels of ultraviolet C (UVC)-induced, irreparable mtDNA damage during early development in Caenorhabditis elegans. This exposure led to life-long reductions in mtDNA copy number and steady-state ATP levels, accompanied by increased oxygen consumption and altered metabolite profiles, suggesting inefficient mitochondrial function. Exposed nematodes were also developmentally delayed, reached smaller adult size, and were rendered more susceptible to subsequent exposure to chemical mitotoxicants. Metabolomic and genetic analysis of key signaling and metabolic pathways supported redox and mitochondrial stress-response signaling during early development as a mechanism for establishing these persistent alterations. Our results highlight the importance of early-life exposures to environmental pollutants, especially in the context of exposure to chemicals that target mitochondria.
|
| 巻・号 |
43
|
| ページ |
102000
|
| 公開日 |
2021-7-1
|
| DOI |
10.1016/j.redox.2021.102000
|
| PII |
S2213-2317(21)00158-0
|
| PMID |
33993056
|
| PMC |
PMC8134077
|
| MeSH |
Animals
Caenorhabditis elegans* / genetics
DNA Damage*
DNA, Mitochondrial / metabolism
Mitochondria / metabolism
Oxidation-Reduction
|
| リソース情報 |
| 線虫 |
tm760
tm776
tm1146 |
