Transcriptome analysis from Nd2-mutant and control fibroblasts

Background: Mutations of mitochondrial (mt)DNA cause a variety of human diseases and are also implicated in ageing processes. Results: Primary fibroblasts of the conplastic mouse strain C57BL/6J-mtALR/LTJ with a mutation at position nt4738 resulting in a single nucleotide exchange (leucine to methionine) in the mitochondrial NADH dehydrogenase subunit 2 (Nd2) gene of the respiratory chain show higher enzyme activity and ATP production and lower ROS production than control fibroblasts. Furthermore, Nd2-mutant fibroblasts show a higher proliferation rate and a reduction of senescence markers. Transcriptome analysis reveals members of the p38MAPK pathway as being significantly downregulated in Nd2-mutant mice as compared with controls. In line with this, inhibition of p38MAPK with SB203580 enhanced the proliferation and reduced cytokine secretion in senescent Nd2-mutant fibroblasts. Conclusion: Taken together, we report Nd2 as a new mitochondrial gene with age-protective function in mice, and possibly in humans, which interferes with age-related signaling pathways. MouseRef-8 v2.0 Expression BeadChips of 8 samples of skin fibroblasts; 4 samples of fibroblasts from 4 mice of C57BL/6J-mtALR/LtJ (Nd2-mutant) and 4 samples of fibroblasts from 4 mice of C57BL/6J-mtAKR/J (control)