RT Journal Article
SR Electronic
T1 Maternal exposure to a mitochondrial toxicant results in life-long alterations in DNA methylation and gene expression in the offspring
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 758474
DO 10.1101/758474
A1 Lozoya, Oswaldo A.
A1 Xu, Fuhua
A1 Grenet, Dagoberto
A1 Wang, Tianyuan
A1 Grimm, Sara A.
A1 Godfrey, Veronica G.
A1 Waidyanatha, Suramya
A1 Woychik, Richard P.
A1 Santos, Janine H.
YR 2019
UL http://biorxiv.org/content/early/2019/09/10/758474.abstract
AB Mitochondrial-driven alterations of the epigenome have been reported but whether they are relevant at the organismal level remain unknown. The viable yellow agouti mouse (Avy) is a powerful epigenetic biosensor model that reports on the DNA methylation status of the Avy locus through the coat color of the animals. Here we show that maternal exposure to rotenone, a potent mitochondrial complex I inhibitor, changes the DNA methylation status of the Avy locus and broadly affects the liver DNA methylome of the offspring. These effects were accompanied by altered gene expression programs that persisted throughout life. Mitochondrial dysfunction was present in the mothers but not in the offspring until 12 months of age, when electron transport and antioxidant defenses were impaired. These results highlight a putative novel role for mitochondria in nuclear epigenetic remodeling during development, raising fundamental questions about the long-term impact of mitochondrial dysfunction to health and disease.