A mutation in the NADH-dehydrogenase subunit 2 suppresses fibroblast aging

Marianne Schauer, Tina Kottek, Madeleine Schönherr, Animesh Bhattacharya, Saleh M. Ibrahim, Misa Hirose, Rüdiger Köhling, Georg Fuellen, Ulf Schmitz, Manfred Kunz

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Mutations of mitochondrial (mt)DNA cause a variety of human diseases and are implicated in premature aging syndromes. Here we investigated a single nucleotide exchange (leucine to methionine) at position nt4738 in the mitochondrial NADH dehydrogenase subunit 2 (Nd2) gene of the respiratory chain. Primary fibroblasts derived from the conplastic mouse strain C57BL/6J-mtALR/LTJ with mutant enzyme, possessed high enzyme activity and ATP production and low ROS production. Furthermore, Nd2-mutant fibroblasts expressed lower senescence markers. Transcriptome analysis revealed that the members of the p38MAPK pathway were significantly downregulated in Nd2-mutant mice. In agreement, inhibition of p38MAPK with SB203580 enhanced proliferation and reduced cytokine secretion in fibroblasts. In Nd2-mutant mouse skin, the amount of Ki67-positive cells was significantly higher than in control skin. The higher amount of Ki67-positive cells and the thicker epidermis in Nd2-mutant mice strongly supported the in vitro data. In conclusion, Nd2 is a mitochondrial gene, involved in age-related signaling pathways.

Original languageBritish English
Pages (from-to)8552-8566
Number of pages15
Issue number11
StatePublished - 2015


  • Aging
  • Mitochondria
  • p38MAPK signalling
  • Senescence
  • Skin fibroblasts


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