Mitochondrial DNA variant in COX1 subunit significantly alters energy metabolism of geographically divergent wild isolates in Caenorhabditis elegans.
Mitochondrial DNA variant in COX1 subunit significantly alters energy metabolism of geographically divergent wild isolates in Caenorhabditis elegans.
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DOI：
10.1016/j.jmb.2014.02.009
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发表时间：
2014-05-29
影响因子：
5.6
通讯作者：
Falk, Marni J.
中科院分区：
文献类型：
--
作者：
Dingley, Stephen D.;Polyak, Erzsebet;Ostrovsky, Julian;Srinivasan, Satish;Lee, Icksoo;Rosenfeld, Amy B.;Tsukikawa, Mai;Xiao, Rui;Selak, Mary A.;Coon, Joshua J.;Hebert, Alexander S.;Grimsrud, Paul A.;Kwon, Young Joon;Pagliarini, David J.;Gai, Xiaowu;Schurr, Theodore G.;Huettemann, Maik;Nakamaru-Ogiso, Eiko;Falk, Marni J.
线粒体DNA（mtDNA）序列变异可以影响复杂疾病的发病率和气候适应性。虽然在地理上定义的人群中进行的研究表明，当mtDNA突变赋予了最适合特定环境的代谢能力时，mtDNA突变就变得固定了，但在哺乳动物中将适应性功能明确分配给特定的mtDNA序列变体一直是一个挑战。我们调查了mtDNA基因组变异是否在功能上影响不同mtDNA谱系和地理起源的秀丽隐杆线虫野生菌株。我们发现，相对于N2（英格兰）野生型线虫，CB 4856野生分离物从一个温暖的本土气候（夏威夷）有一个独特的p.A12 S氨基酸取代的线粒体DNA编码的COX 1核心催化亚基的线粒体复合物IV（CIV）。相对于N2，在20 °C下生长的CB 4856蠕虫具有显著增加的CIV酶活性、线粒体基质氧化剂负荷和对氧化应激的敏感性，但具有显著降低的寿命和线粒体膜电位。有趣的是，在25 °C的自然温度下生长的CB 4856中，线粒体膜电位显著增加。一个跨线粒体胞质杂交虫株chpIR（M，CB 4856> N2）被培育为在N2核背景中与CB 4856 mtDNA基因组同质。胞质杂交体菌株还显示出显著增加的CIV活性，表明这种差异是由mtDNA编码的p.A12S变体引起的。然而，chpIR（M，CB 4856> N2）蠕虫相对于CB 4856具有显著降低的中值和最大寿命，这可能与它们的核- mtDNA基因组错配有关。总的来说，这些数据表明，C。不同地理来源的线虫野生分离株可能通过mtDNA变异来调节线粒体能量代谢的关键方面，从而适应环境挑战。
Mitochondrial DNA (mtDNA) sequence variation can influence the penetrance of complex diseases and climatic adaptation. While studies in geographically defined human populations suggest that mtDNA mutations become fixed when they have conferred metabolic capabilities optimally suited for a specific environment, it has been challenging to definitively assign adaptive functions to specific mtDNA sequence variants in mammals. We investigated whether mtDNA genome variation functionally influences Caenorhabditis elegans wild isolates of distinct mtDNA lineages and geographic origins. We found that, relative to N2 (England) wild-type nematodes, CB4856 wild isolates from a warmer native climate (Hawaii) had a unique p.A12S amino acid substitution in the mtDNA-encoded COX1 core catalytic subunit of mitochondrial complex IV (CIV). Relative to N2, CB4856 worms grown at 20 °C had significantly increased CIV enzyme activity, mitochondrial matrix oxidant burden, and sensitivity to oxidative stress but had significantly reduced lifespan and mitochondrial membrane potential. Interestingly, mitochondrial membrane potential was significantly increased in CB4856 grown at its native temperature of 25 °C. A transmitochondrial cybrid worm strain, chpIR (M, CB4856 > N2), was bred as homoplasmic for the CB4856 mtDNA genome in the N2 nuclear background. The cybrid strain also displayed significantly increased CIV activity, demonstrating that this difference results from the mtDNA-encoded p.A12S variant. However, chpIR (M, CB4856 > N2) worms had significantly reduced median and maximal lifespan relative to CB4856, which may relate to their nuclear– mtDNA genome mismatch. Overall, these data suggest that C. elegans wild isolates of varying geographic origins may adapt to environmental challenges through mtDNA variation to modulate critical aspects of mitochondrial energy metabolism.
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DOI：
10.1042/bj20130029
发表时间：
2013-10-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Fetterman JL;Zelickson BR;Johnson LW;Moellering DR;Westbrook DG;Pompilius M;Sammy MJ;Johnson M;Dunham-Snary KJ;Cao X;Bradley WE;Zhang J;Wei CC;Chacko B;Schurr TG;Kesterson RA;Dell'italia LJ;Darley-Usmar VM;Welch DR;Ballinger SW
通讯作者：
Ballinger SW
DOI：
10.1098/rspb.2009.0752
发表时间：
2009-10-07
期刊：
Proceedings. Biological sciences
影响因子：
--
作者：
Balloux F;Handley LJ;Jombart T;Liu H;Manica A
通讯作者：
Manica A
影响因子：
9.2
作者：
Falk, Marni J.;Kayser, Ernst-Bernhard;Sedensky, Margaret M.
通讯作者：
Sedensky, Margaret M.
DOI：
10.1073/pnas.0804253105
发表时间：
2008-10-14
影响因子：
11.1
作者：
Ellison, Christopher K.;Burton, Ronald S.
通讯作者：
Burton, Ronald S.
影响因子：
3.3
作者：
Flibotte, Stephane;Edgley, Mark L.;Moerman, Donald G.
通讯作者：
Moerman, Donald G.