Expression of the yeast NADH dehydrogenase Ndi1 in Drosophila confers increased lifespan independently of dietary restriction

Alberto Sanz, Mikko Soikkeli, Manuel Portero-Otin, Angela Wilson, Esko Kemppainen, George David McIlroy, Simo Ellila, Kia K. Kemppainen, Tea Tuomela, Matti Lakanmaa, Essi Kiviranta, Rhoda Stefanatos, Eric Dufour, Bettina Hutz, Alba Naudi, Mariona Jove, Akbar Zeb, Suvi Vartiainen, Akemi Matsuno-Yagi, Takao YagiPierre Rustin, Reineld Pamplona, Howard T. Jacobs

Research output: Contribution to journalArticle

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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.
Original languageEnglish
Pages (from-to)9105-9110
Number of pages6
JournalPNAS
Volume107
Issue number20
DOIs
Publication statusPublished - 18 May 2010

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NADH Dehydrogenase
Oxidative Phosphorylation
Diptera
Drosophila
Yeasts
Rotenone
Enzymes
RNA Interference
NAD
Reactive Oxygen Species
Oxidative Stress
Pathology
Mutation
Growth

Keywords

  • aging
  • mitochondria
  • respiratory chain
  • free radicals

Cite this

Expression of the yeast NADH dehydrogenase Ndi1 in Drosophila confers increased lifespan independently of dietary restriction. / Sanz, Alberto; Soikkeli, Mikko; Portero-Otin, Manuel; Wilson, Angela; Kemppainen, Esko; McIlroy, George David; Ellila, Simo; Kemppainen, Kia K.; Tuomela, Tea; Lakanmaa, Matti; Kiviranta, Essi; Stefanatos, Rhoda; Dufour, Eric; Hutz, Bettina; Naudi, Alba; Jove, Mariona; Zeb, Akbar; Vartiainen, Suvi; Matsuno-Yagi, Akemi; Yagi, Takao; Rustin, Pierre; Pamplona, Reineld; Jacobs, Howard T.

In: PNAS, Vol. 107, No. 20, 18.05.2010, p. 9105-9110.

Research output: Contribution to journalArticle

Sanz, A, Soikkeli, M, Portero-Otin, M, Wilson, A, Kemppainen, E, McIlroy, GD, Ellila, S, Kemppainen, KK, Tuomela, T, Lakanmaa, M, Kiviranta, E, Stefanatos, R, Dufour, E, Hutz, B, Naudi, A, Jove, M, Zeb, A, Vartiainen, S, Matsuno-Yagi, A, Yagi, T, Rustin, P, Pamplona, R & Jacobs, HT 2010, 'Expression of the yeast NADH dehydrogenase Ndi1 in Drosophila confers increased lifespan independently of dietary restriction', PNAS, vol. 107, no. 20, pp. 9105-9110. https://doi.org/10.1073/pnas.0911539107
Sanz, Alberto ; Soikkeli, Mikko ; Portero-Otin, Manuel ; Wilson, Angela ; Kemppainen, Esko ; McIlroy, George David ; Ellila, Simo ; Kemppainen, Kia K. ; Tuomela, Tea ; Lakanmaa, Matti ; Kiviranta, Essi ; Stefanatos, Rhoda ; Dufour, Eric ; Hutz, Bettina ; Naudi, Alba ; Jove, Mariona ; Zeb, Akbar ; Vartiainen, Suvi ; Matsuno-Yagi, Akemi ; Yagi, Takao ; Rustin, Pierre ; Pamplona, Reineld ; Jacobs, Howard T. / Expression of the yeast NADH dehydrogenase Ndi1 in Drosophila confers increased lifespan independently of dietary restriction. In: PNAS. 2010 ; Vol. 107, No. 20. pp. 9105-9110.
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AU - McIlroy, George David

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AU - Kemppainen, Kia K.

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AU - Stefanatos, Rhoda

AU - Dufour, Eric

AU - Hutz, Bettina

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AU - Jove, Mariona

AU - Zeb, Akbar

AU - Vartiainen, Suvi

AU - Matsuno-Yagi, Akemi

AU - Yagi, Takao

AU - Rustin, Pierre

AU - Pamplona, Reineld

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N2 - 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.

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