Biological and epigenetic alterations of mitochondria involved in cellular replicative and hydrogen peroxide-induced premature senescence of human embryonic lung fibroblasts.

ABSTRACT

The mitoepigenetic modifications may be closely related to cellular fate. Both the replicative and hydrogen peroxide (H2O2)-induced premature senescence models were used to detect the mitochondrial biological characteristics and the epigenetic factors during senescence of human embryonic lung fibroblasts. The mitochondrial quantity was decreased in two senescence stages, while the mitochondrial DNA (mtDNA) copy number was increased significantly and the methyltransferases activity likewise. And the acute mtROS accumulation could launch premature senescence. Later, the persistent premature senescence owned the higher level of adenosine triphosphate (ATP) and mitochondrial 5-methylcytosine (mt-5-mC), and the less level of 8-hydroxydeoxyguanosine (8-OHdG) than those of replicative senescence. The mtDNA methylation-related enzymes, binding protein and the mitochondrial transcription regulators presented the differentially expressed profiles in both senescent states. Interestingly, the hypermethylation in the CpG region of mitochondrial transcription factor B2 (TFB2M) contributed to its downregulation of mRNA level in replicative senescence. The alterations of the mitochondrial biological functions and mtDNA features would be novel candidate biomarkers involved in cellular senescence. The specific methylation status of mtDNA may also have a crosstalk with oxidative stress to the mitochondrial function, contributing to cellular senescence.