Lopes João, Pinto Maria Joana, Rodrigues Aurora, Vasconcelos Filipe, Oliveira Rui
CBMA (Centre of Molecular and Environmental Biology)/ Department of Biology, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
Open Microbiol J. 2010 Aug 17;4:75-82. doi: 10.2174/1874285801004010075.
Mammalian electron transfer flavoproteins comprise a mitochondrial matrix heterodimer, and an electron transfer flavoprotein dehydrogenase localized in the mitochondrial inner membrane. Electrons from primary acyl-CoA dehydrogenases, of mitochondrial metabolism of fatty acids and amino acids, are transferred to the matricial heterodimer and, subsequently, to the electron transfer flavoprotein dehydrogenase, which transfers electrons to ubiquinone of the mitochondrial electron transport chain. Several evidences suggest that these proteins may convey electrons directly to molecular oxygen, yielding reactive oxygen species. In this work, we investigated phenotypes of the yeast mutants affected in the orthologous genes of the matrix heterodimer (AIM45 and YGR207c/CIR1) and of the electron transfer flavoprotein dehydrogenase (YOR356w/CIR2). The mutant strains aim45 and yor356w/cir2 displayed better growth on several non-fermentable carbon sources, which depended on the component of the electron transport chain that accepts the electrons resulting from its mitochondrial oxidation. Furthermore, upon heat shock, the mutant strains presented decreased intracellular oxidation, suggesting that these flavoproteins are a source of reactive oxygen species. Other phenotypes identified suggest that AIM45, YGR207c/CIR1 and YOR356w/CIR2 can protect cells from oxidative and heat stress, which encompass increased heat stress sensitivity, superoxide sensitivity, both only on non-fermentable carbon sources.
哺乳动物电子传递黄素蛋白包括一种线粒体基质异二聚体和一种定位于线粒体内膜的电子传递黄素蛋白脱氢酶。来自脂肪酸和氨基酸线粒体代谢的初级酰基辅酶A脱氢酶的电子，被转移到基质异二聚体，随后转移到电子传递黄素蛋白脱氢酶，该酶将电子转移到线粒体电子传递链的泛醌。一些证据表明，这些蛋白质可能直接将电子传递给分子氧，产生活性氧。在这项工作中，我们研究了在基质异二聚体（AIM45和YGR207c/CIR1）和电子传递黄素蛋白脱氢酶（YOR356w/CIR2）的直系同源基因中受影响的酵母突变体的表型。突变菌株aim45和yor356w/cir2在几种非发酵碳源上生长得更好，这取决于接受其线粒体氧化产生的电子的电子传递链的组成部分。此外，在热休克后，突变菌株的细胞内氧化减少，表明这些黄素蛋白是活性氧的来源。鉴定出的其他表型表明，AIM45、YGR207c/CIR1和YOR356w/CIR2可以保护细胞免受氧化和热应激，这包括仅在非发酵碳源上增加的热应激敏感性、超氧化物敏感性。
