Nmdmc overexpression extends Drosophila lifespan and reduces levels of mitochondrial reactive oxygen species

Biochem Biophys Res Commun. 2015 Oct 2;465(4):845-50. doi: 10.1016/j.bbrc.2015.08.098. Epub 2015 Aug 28.

Abstract

NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase (NMDMC) is a bifunctional enzyme involved in folate-dependent metabolism and highly expressed in rapidly proliferating cells. However, Nmdmc physiological roles remain unveiled. We found that ubiquitous Nmdmc overexpression enhanced Drosophila lifespan and stress resistance. Interestingly, Nmdmc overexpression in the fat body was sufficient to increase lifespan and tolerance against oxidative stress. In addition, these conditions coincided with significant decreases in the levels of mitochondrial ROS and Hsp22 as well as with a significant increase in the copy number of mitochondrial DNA. These results suggest that Nmdmc overexpression should be beneficial for mitochondrial homeostasis and increasing lifespan.

Keywords: Drosophila; Longevity; Mitochondrial DNA; NMDMC; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminohydrolases / genetics*
  • Aminohydrolases / metabolism*
  • Animals
  • Animals, Genetically Modified
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism*
  • Fat Body / metabolism
  • Female
  • Genes, Insect
  • Longevity / genetics*
  • Longevity / physiology*
  • Male
  • Methylenetetrahydrofolate Dehydrogenase (NADP) / genetics*
  • Methylenetetrahydrofolate Dehydrogenase (NADP) / metabolism*
  • Mitochondria / metabolism
  • Multienzyme Complexes / genetics*
  • Multienzyme Complexes / metabolism*
  • Mutation
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Up-Regulation

Substances

  • DNA, Mitochondrial
  • Drosophila Proteins
  • Multienzyme Complexes
  • Reactive Oxygen Species
  • methylene tetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase
  • Methylenetetrahydrofolate Dehydrogenase (NADP)
  • Aminohydrolases