Drosophila sbo regulates lifespan through its function in the synthesis of coenzyme Q in vivo

Jiyong Liu^{a, b},
Qinghua Wu^{a, b},
Dianlu He^a,
Tengyu Ma^a,
Li Du^a,
Wen Dui^{a, b},
Xiaoyan Guo^{a, c},
Renjie Jiao^{a
, ,}

a.
State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
b.
Graduate School of the Chinese Academy of Sciences, Beijing 100080, China
c.
Department of Biology, Texas A&M University, College Station, TX 77843, USA

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Corresponding author: E-mail address: rjiao@sun5.ibp.ac.cn (Renjie Jiao)

摘要

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Abstract: CoQ is an essential electron carrier in the mitochondrial respiratory chain of both eukaryotes and prokaryotes. It consists of a benzoquinone head group and a hydrophobic polyisoprenoid tail. The genes (COQ1–9) involved in CoQ biosynthesis have been characterized in yeast. In this study, we generated and molecularly characterized a mutant allele of a novel Drosophila gene, sbo, which encodes a protein that is predicted to catalyze the prenylation of p-hydroxybenzoate with the isoprenoid chain during the process of CoQ synthesis. Expression of sbo in yeast rescues the lethality of ∆COQ2 mutant cells, indicating that sbo is a functional homolog of COQ2. HPLC results show that the levels of CoQ₉ and CoQ₁₀ were significantly reduced in sbo heterozygous adult flies. Furthermore, the mean lifespans of males and females heterozygous for sbo are extended by 12.5% and 30.8%, respectively. Homozygous sbo animals exhibit reduced activities of the insulin/insulin-like growth factor signaling (IIS) pathway. Taken together, we conclude that sbo is an essential gene for Drosophila development, mutation of which leads to an extension of lifespan most likely by altering endogenous CoQ biosynthesis.
- Coenzyme Q /
- Lifespan /
- Insulin signaling

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参考文献(50)

[1]	Artuch, R., Salviati, L., Jackson, S. et al. Coenzyme Q10 deficiencies in neuromuscular diseases Adv. Exp. Med. Biol., 652 (2009),pp. 117-128
[2]	Ashby, M.N., Kutsunai, S.Y., Ackerman, S. et al. J. Biol. Chem., 267 (1992),pp. 4128-4136
[3]	Bader, M., Muse, W., Ballou, D.P. et al. Oxidative protein folding is driven by the electron transport system Cell, 98 (1999),pp. 217-227
[4]	Battino, M., Gorini, A., Villa, R.F. et al. Coenzyme Q content in synaptic and non-synaptic mitochondria from different brain regions in the ageing rat Mech. Ageing Dev., 78 (1995),pp. 173-187
[5]	Bauer, J.H., Chang, C., Morris, S.N.S. et al. Expression of dominant-negative Dmp53 in the adult fly brain inhibits insulin signaling Proc. Natl. Acad. Sci. USA, 104 (2007),pp. 13355-13360
[6]	Beyer, R.E., Burnett, B.A., Cartwright, K.J. et al. Tissue coenzyme Q (ubiquinone) and protein concentrations over the life span of the laboratory rat Mech. Ageing Dev., 32 (1985),pp. 267-281
[7]	Bohni, R., Riesgo-Escovar, J., Oldham, S. et al. Cell, 97 (1999),pp. 865-875
[8]	Britton, J.S., Lockwood, W.K., Li, L. et al. Dev. Cell, 2 (2002),pp. 239-249
[9]	Clancy, D.J., Gems, D., Harshman, L.G. et al. Science, 292 (2001),pp. 104-106
[10]	Copeland, J.M., Cho, J., , Hur, J.H. et al. Curr. Biol., 19 (2009),pp. 1591-1598
[11]	Crane, F.L., Hatefi, Y., Lester, R.L. et al. Isolation of a quinone from beef heart mitochondria Biochim. Biophys. Acta, 25 (1957),pp. 220-221
[12]	Cristina, D., Cary, M., Lunceford, A. et al. PLoS Genet., 5 (2009),p. e1000450
[13]	Dillin, A., Hsu, A.L., Arantes-Oliveira, N.A. et al. Rates of behavior and aging specified by mitochondrial function during development Science, 298 (2002),pp. 2398-2401
[14]	Edgar, B.A. How flies get their size: genetics meets physiology Nat. Rev. Genet., 7 (2006),pp. 907-916
[15]	Emanuelsson, O., Nielsen, H., Brunak, S. et al. Predicting subcellular localization of proteins based on their N-terminal amino acid sequence J. Mol. Biol., 300 (2000),pp. 1005-1016
[16]	Ernster, L., Dallner, G. Biochemical, physiological and medical aspects of ubiquinone function Biochim. Biophys. Acta, 1271 (1995),pp. 195-204
[17]	Feany, M.B., Bender, W.W. Nature, 404 (2000),pp. 394-398
[18]	Feng, J.L., Bussiere, F., Hekimi, S. Dev. Cell, 1 (2001),pp. 633-644
[19]	Finn, R.D., Mistry, J., Tate, J. et al. The Pfam protein families database Nucleic Acids Res., 38 (2010),pp. D211-D222
[20]	Forsgren, M., Attersand, A., Lake, S. et al. Biochem. J., 382 (2004),pp. 519-526
[21]	Fuss, B., Becker, T., Zinke, I. et al. Nature, 444 (2006),pp. 945-948
[22]	Ganetzky, B., Flanagan, J.R. Exp. Gerontol., 13 (1978),pp. 189-196
[23]	Gargano, J.W., Martin, I., Bhandari, P. et al. Exp. Gerontol., 40 (2005),pp. 386-395
[24]	Hyun, S., Lee, J.H., Jin, H. et al. Conserved microRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K Cell, 139 (2009),pp. 1096-1108
[25]	Ishii, N., Senoo-Matsuda, N., Miyake, K. et al. Mech. Ageing Dev., 125 (2004),pp. 41-46
[26]	Jonassen, T., Clarke, C.F. J. Biol. Chem., 275 (2000),pp. 12381-12387
[27]	Jonassen, T., Larsen, P.L., Clarke, C.F. Proc. Natl. Acad. Sci. USA, 98 (2001),pp. 421-426
[28]	Kalen, A., Appelkvist, E.L., Dallner, G. Age-related changes in the lipid compositions of rat and human tissues Lipids, 24 (1989),pp. 579-584
[29]	Kawamukai, M. Biotechnol. Appl. Biochem., 53 (2009),pp. 217-226
[30]	Larsen, P.L., Clarke, C.F. Science, 295 (2002),pp. 120-123
[31]	Lass, A., Kwong, L., Sohal, R.S. Mitochondrial coenzyme Q content and aging Biofactors, 9 (1999),pp. 199-205
[32]	Levavasseur, F., Miyadera, H., Sirois, J. et al. Ubiquinone is necessary for mouse embryonic development but is not essential for mitochondrial respiration J. Biol. Chem., 276 (2001),pp. 46160-46164
[33]	Liu, X.X., Jiang, N., Hughes, B. et al. Gene Dev., 19 (2005),pp. 2424-2434
[34]	Palmer, M.R., Sackton, T.B. Aging Cell, 2 (2003),pp. 335-339
[35]	Park, J., Lee, S.B., Lee, S. et al. Nature, 441 (2006),pp. 1157-1161
[36]	Pepe, S., Marasco, S.F., Haas, S.J. et al. Mitochondrion, 7 (2007),pp. S154-S167
[37]	Rera, M., Monnier, V., Tricoire, H. Mech. Ageing Dev., 131 (2010),pp. 156-164
[38]	Sacconi, S., Trevisson, E., Salviati, L. et al. Neuromuscular Disord., 20 (2010),pp. 44-48
[39]	Samuelson, A.V., Carr, C.E., Ruvkun, G. Gene Dev., 21 (2007),pp. 2976-2994
[40]	Slack, C., Werz, C., Wieser, D. et al. PLoS Genet., 6 (2010),p. e1000881
[41]	Sohal, R.S., Forster, M.J. Coenzyme Q, oxidative stress and aging Mitochondrion, 7 (2007),pp. S103-S111
[42]	Sonnhammer, E.L., von Heijne, G., Krogh, A. A hidden Markov model for predicting transmembrane helices in protein sequences Proc. Int. Conf. Intell. Syst. Mol. Biol., 6 (1998),pp. 175-182
[43]	Suzuki, K., Okada, K., Kamiya, Y. et al. J. Biochem., 121 (1997),pp. 496-505
[44]	Taguchi, A., White, M.F. Insulin-like signaling, nutrient homeostasis, and life span Annu. Rev. Physiol., 70 (2008),pp. 191-212
[45]	Turunen, M., Olsson, J., Dallner, G. Metabolism and function of coenzyme Q Biochim. Biophys. Acta, 1660 (2004),pp. 171-199
[46]	Werz, C., Kohler, K., Hafen, E. et al. PLoS Genet., 5 (2009),p. e1000596
[47]	Winrow, M.J., Rudney, H. Biochem. Biophys. Res. Commun., 37 (1969),pp. 833-840
[48]	Wong, A., Boutis, P., Hekimi, S. Genetics, 139 (1995),pp. 1247-1259
[49]	Yazaki, K., Kunihisa, M., Fujisaki, T. et al. J. Biol. Chem., 277 (2002),pp. 6240-6246
[50]	Zinke, I., Kirchner, C., Chao, L.C. et al. Development, 126 (1999),pp. 5275-5284