Expression of the Ciona intestinalis Alternative Oxidase (AOX) in Drosophila Complements Defects in Mitochondrial Oxidative Phosphorylation

被引：146

作者：

Fernandez-Ayala, Daniel J. M. ^{[1
,2
,3
]}

Sanz, Alberto ^{[1
,2
]}

Vartiainen, Suvi ^{[1
,2
]}

Kemppainen, Kia K. ^{[1
,2
]}

Babusiak, Marek ^{[1
,2
]}

Mustalahti, Eero ^{[1
,2
]}

Costa, Rodolfo ^{[4
]}

Tuomela, Tea ^{[1
,2
]}

Zeviani, Massimo ^{[5
]}

Chung, Jongkyeong ^{[6
]}

O'Dell, Kevin M. C. ^{[7
]}

Rustin, Pierre ^{[8
,9
]}

Jacobs, Howard T. ^{[1
,2
,7
]}

机构：

[1] Univ Tampere, Inst Med Technol, Tampere 33014, Finland

[2] Univ Tampere, Tampere Univ Hosp, Tampere 33014, Finland

[3] Univ Pablo Olavide, CSIC, CABD, Seville 41013, Spain

[4] Univ Padua, Dept Biol, I-35131 Padua, Italy

[5] Natl Inst Neurol C Besta, Div Mol Neurogenet, I-20126 Milan, Italy

[6] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea

[7] Univ Glasgow, IBLS Div Mol Genet, Glasgow G11 6NU, Lanark, Scotland

[8] Hop Robert Debre, INSERM, U676, F-75870 Paris, France

[9] Univ Paris 07, Fac Med Denis Diderot, F-75870 Paris, France

来源：

CELL METABOLISM | 2009年 / 9卷 / 05期

关键词：

CYTOCHROME-C-OXIDASE; PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; DJ-1; MUTANTS; STRESS; RESPIRATION; MODEL; DISORDERS; SURF1; OVEREXPRESSION;

D O I：

10.1016/j.cmet.2009.03.004

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Defects in mitochondrial OXPHOS are associated with diverse and mostly intractable human disorders. The single-subunit alternative oxidase (AOX) found in many eukaryotes, but not in arthropods or vertebrates, offers a potential bypass of the OXPHOS cytochrome chain under conditions of pathological OXPHOS inhibition. We have engineered Ciona intestinalis AOX for conditional expression in Drosophila melanogaster. Ubiquitous AOX expression produced no detrimental phenotype in wild-type flies. However, mitochondrial suspensions from AOX-expressing flies exhibited a significant cyanide-resistant substrate oxidation, and the flies were partially resistant to both cyanide and antimycin. AOX expression was able to complement the semilethality of partial knockdown of both cyclope (COXVIc) and the complex IV assembly factor Surf1. It also rescued the locomotor defect and excess mitochondrial ROS production of flies mutated in dj-1 beta, a Drosophila homolog of the human Parkinson's disease gene DJ1. AOX appears to offer promise as a wide-spectrum therapeutic tool in OXPHOS disorders.

引用

页码：449 / 460

页数：12

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