Natural variation in life history and aging phenotypes is associated with mitochondrial DNA deletion frequency in Caenorhabditis briggsae.
Natural variation in life history and aging phenotypes is associated with mitochondrial DNA deletion frequency in Caenorhabditis briggsae.
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DOI：
10.1186/1471-2148-11-11
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发表时间：
2011-01-12
影响因子：
3.4
通讯作者：
Denver DR
中科院分区：
文献类型：
--
作者：
Estes S;Coleman-Hulbert AL;Hicks KA;de Haan G;Martha SR;Knapp JB;Smith SW;Stein KC;Denver DR
损害线粒体功能的突变与多种代谢和年龄相关疾病相关。对线粒体功能障碍在衰老过程中的作用进行严格测试的障碍是缺乏具有相关的、自然发生的线粒体遗传变异的模型系统。为了开发这样一个模型系统的目标，我们研究了自然变化的生活史，代谢和老化表型，因为它涉及到一个自然发生的异质性线粒体ND5缺失的水平最近发现分离的野生种群的土壤线虫，细杆线虫Briggsae。ND5的正常产物是线粒体电子传递链的中心组分，并且是细胞能量代谢的组成部分。我们量化了C. Briggsae分离株的所有表型测量，只有其中一些是统计学上与分离株特异性ND5缺失频率。结果表明，ND5缺失水平与繁殖力相关性状和咽泵率呈显著负相关。具有高ND5缺失水平的Briggsae分离株经历了早期生殖力和寿命之间的权衡。相反，氧化应激抗性仅与ND5缺失水平弱相关，而ATP含量与缺失水平无关。最后，体内测量的活性氧自由基的平均水平与ND 5缺失水平呈显着的非线性关系，这种模式可能是由抗氧化剂或其他补偿机制的分离株间差异驱动的。我们的研究结果表明，ND5缺失可能会对健康和线粒体功能产生不利影响，同时促进自然种群的衰老，并有助于进一步建立该物种作为明确测试衰老生物学和线粒体遗传学假设的有用模型。
Mutations that impair mitochondrial functioning are associated with a variety of metabolic and age-related disorders. A barrier to rigorous tests of the role of mitochondrial dysfunction in aging processes has been the lack of model systems with relevant, naturally occurring mitochondrial genetic variation. Toward the goal of developing such a model system, we studied natural variation in life history, metabolic, and aging phenotypes as it relates to levels of a naturally-occurring heteroplasmic mitochondrial ND5 deletion recently discovered to segregate among wild populations of the soil nematode, Caenorhabditis briggsae. The normal product of ND5 is a central component of the mitochondrial electron transport chain and integral to cellular energy metabolism. We quantified significant variation among C. briggsae isolates for all phenotypes measured, only some of which was statistically associated with isolate-specific ND5 deletion frequency. We found that fecundity-related traits and pharyngeal pumping rate were strongly inversely related to ND5 deletion level and that C. briggsae isolates with high ND5 deletion levels experienced a tradeoff between early fecundity and lifespan. Conversely, oxidative stress resistance was only weakly associated with ND5 deletion level while ATP content was unrelated to deletion level. Finally, mean levels of reactive oxygen species measured in vivo showed a significant non-linear relationship with ND5 deletion level, a pattern that may be driven by among-isolate variation in antioxidant or other compensatory mechanisms. Our findings suggest that the ND5 deletion may adversely affect fitness and mitochondrial functioning while promoting aging in natural populations, and help to further establish this species as a useful model for explicit tests of hypotheses in aging biology and mitochondrial genetics.
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DOI：
10.1042/bj20081386
发表时间：
2009-01-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Murphy MP
通讯作者：
Murphy MP
影响因子：
9.8
作者：
Hillier LW;Miller RD;Baird SE;Chinwalla A;Fulton LA;Koboldt DC;Waterston RH
通讯作者：
Waterston RH
DOI：
10.1073/pnas.0400848101
发表时间：
2004-05-25
影响因子：
11.1
作者：
Huang, C;Xiong, CJ;Kornfeld, K
通讯作者：
Kornfeld, K
影响因子：
4.9
作者：
Cutter, Asher D.;Yan, Weiang;Felix, Marie-Anne
通讯作者：
Felix, Marie-Anne
影响因子：
3.3
作者：
Howe, Dana K.;Baer, Charles F.;Denver, Dee R.
通讯作者：
Denver, Dee R.