Restoration of electron transport without proton pumping in mammalian mitochondria

被引:63
作者
Perales-Clemente, Ester [1 ]
Pilar Bayona-Bafaluy, Maria [1 ]
Perez-Martos, Acisclo [1 ]
Barrientos, Antoni [2 ,3 ]
Fernandez-Silva, Patricio [1 ]
Antonio Enriquez, Jose [1 ]
机构
[1] Univ Zaragoza, Dept Bioquim, E-50013 Zaragoza, Spain
[2] Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn Ctr Med Genet, Dept Neurol, Miami, FL 33136 USA
[3] Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn Ctr Med Genet, Dept Biochem & Mol Biol, Miami, FL 33136 USA
关键词
AOX; mouse; oxidative phosphorylation; NDI1; CoQ;
D O I
10.1073/pnas.0810518105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have restored the CoQ oxidative capacity of mouse mtDNA-less cells (p cells) by transforming them with the alternative oxidase Aox of Emericella nidulans. Cotransforming p cells with the NADH dehydrogenase of Saccharomyces cerevisiae, Ndi1 and Aox recovered the NADH DH/CoQ reductase and the CoQ oxidase activities. CoQ oxidation by AOX reduces the dependence of rho degrees cells on pyruvate and uridine. Coexpression of AOX and NDI1 further improves the recycling of NAD(+). Therefore, 2 single-protein enzymes restore the electron transport in mammalian mitochondria substituting >80 nuclear DNA-encoded and 11 mtDNA-encoded proteins. Because those enzymes do not pump protons, we were able to split electron transport and proton pumping (ATP synthesis) and inquire which of the metabolic deficiencies associated with the loss of oxidative phosphorylation should be attributed to each of the 2 processes.
引用
收藏
页码:18735 / 18739
页数:5
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