Back to Search
Start Over
Expression of the yeast NADH dehydrogenase Ndi1 in Drosophila confers increased lifespan independently of dietary restriction
- Source :
- Proceedings of the National Academy of Sciences. 107:9105-9110
- Publication Year :
- 2010
- Publisher :
- Proceedings of the National Academy of Sciences, 2010.
-
Abstract
- Mutations in mitochondrial oxidative phosphorylation complex I are associated with multiple pathologies, and complex I has been proposed as a crucial regulator of animal longevity. In yeast, the single-subunit NADH dehydrogenase Ndi1 serves as a non-proton-translocating alternative enzyme that replaces complex I, bringing about the reoxidation of intramitochondrial NADH. We have created transgenic strains of Drosophila that express yeast NDI1 ubiquitously. Mitochondrial extracts from NDI1 -expressing flies displayed a rotenone-insensitive NADH dehydrogenase activity, and functionality of the enzyme in vivo was confirmed by the rescue of lethality resulting from RNAi knockdown of complex I. NDI1 expression increased median, mean, and maximum lifespan independently of dietary restriction, and with no change in sirtuin activity. NDI1 expression mitigated the aging associated decline in respiratory capacity and the accompanying increase in mitochondrial reactive oxygen species production, and resulted in decreased accumulation of markers of oxidative damage in aged flies. Our results support a central role of mitochondrial oxidative phosphorylation complex I in influencing longevity via oxidative stress, independently of pathways connected to nutrition and growth signaling.
- Subjects :
- Aging
Saccharomyces cerevisiae Proteins
Blotting, Western
Longevity
Respiratory chain
Oxidative phosphorylation
Mitochondrion
medicine.disease_cause
NADH dehydrogenase activity
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Caloric Restriction
030304 developmental biology
2. Zero hunger
0303 health sciences
Electron Transport Complex I
Multidisciplinary
biology
Histocytochemistry
Reverse Transcriptase Polymerase Chain Reaction
NADH dehydrogenase
Biological Sciences
Mitochondria
Oxidative Stress
Drosophila melanogaster
Biochemistry
Sirtuin
biology.protein
RNA Interference
Reactive Oxygen Species
030217 neurology & neurosurgery
Oxidative stress
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 107
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....0b6b82970c8765c60f5900d4c5235228