Early-life mitochondrial DNA damage results in lifelong deficits in energy production mediated by redox signaling in Caenorhabditis elegans.
Early-life mitochondrial DNA damage results in lifelong deficits in energy production mediated by redox signaling in Caenorhabditis elegans.
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DOI：
10.1016/j.redox.2021.102000
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发表时间：
2021-07
期刊：
影响因子：
11.4
通讯作者：
Meyer JN
中科院分区：
文献类型：
--
作者：
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
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. Early life mtDNA damage led to lifelong deficits in mitochondrial function. C. elegans developed slowly and were sensitive to chemical exposures as adults. Redox signaling is a mechanism that establishes these persistent alterations. Data are consistent with the Developmental Origins of Health and Disease model.
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影响因子：
6.1
作者：
Berthiaume, J. M.;Wallace, K. B.
通讯作者：
Wallace, K. B.
影响因子：
14.9
作者：
Bess AS;Crocker TL;Ryde IT;Meyer JN
通讯作者：
Meyer JN
DOI：
10.1186/1476-069x-11-42
发表时间：
2012-06-27
期刊：
Environmental health : a global access science source
影响因子：
--
作者：
Barouki R;Gluckman PD;Grandjean P;Hanson M;Heindel JJ
通讯作者：
Heindel JJ
影响因子：
4.5
作者：
Ferrara CT;Wang P;Neto EC;Stevens RD;Bain JR;Wenner BR;Ilkayeva OR;Keller MP;Blasiole DA;Kendziorski C;Yandell BS;Newgard CB;Attie AD
通讯作者：
Attie AD
影响因子：
9.2
作者：
Falk, Marni J.;Kayser, Ernst-Bernhard;Sedensky, Margaret M.
通讯作者：
Sedensky, Margaret M.