Department of Biological Sciences, University of South Carolina, 700 Sumter Street, Columbia, SC, 29208, USA.
School of Earth Sciences and Environmental Engineering, Gwangju Institute of Science and Technology, Gwangju, 61005, Korea.
Sci Rep. 2022 Feb 11;12(1):2354. doi: 10.1038/s41598-022-06279-4.
Macromolecular damage leading to cell, tissue and ultimately organ dysfunction is a major contributor to aging. Intracellular reactive oxygen species (ROS) resulting from normal metabolism cause most damage to macromolecules and the mitochondria play a central role in this process as they are the principle source of ROS. The relationship between naturally occurring variations in the mitochondrial (MT) genomes leading to correspondingly less or more ROS and macromolecular damage that changes the rate of aging associated organismal decline remains relatively unexplored. MT complex I, a component of the electron transport chain (ETC), is a key source of ROS and the NADH dehydrogenase subunit 5 (ND5) is a highly conserved core protein of the subunits that constitute the backbone of complex I. Using Daphnia as a model organism, we explored if the naturally occurring sequence variations in ND5 correlate with a short or long lifespan. Our results indicate that the short-lived clones have ND5 variants that correlate with reduced complex I activity, increased oxidative damage, and heightened expression of ROS scavenger enzymes. Daphnia offers a unique opportunity to investigate the association between inherited variations in components of complex I and ROS generation which affects the rate of aging and lifespan.
大分子损伤导致细胞、组织,最终导致器官功能障碍,是衰老的主要原因。正常代谢产生的细胞内活性氧(ROS)对大分子造成的大多数损伤,而线粒体在这个过程中起着核心作用,因为它们是 ROS 的主要来源。线粒体(MT)基因组中自然发生的变异导致相应较少或较多的 ROS 和大分子损伤,从而改变与衰老相关的生物体下降的速度,这一关系仍然相对未被探索。线粒体复合体 I 是电子传递链(ETC)的一个组成部分,是 ROS 的主要来源,而 NADH 脱氢酶亚单位 5(ND5)是构成复合体 I 骨干的亚单位的高度保守核心蛋白。我们使用水蚤作为模型生物,探索了 ND5 中的自然发生的序列变异是否与短寿命或长寿命相关。我们的结果表明,寿命较短的克隆具有与复合体 I 活性降低、氧化损伤增加以及 ROS 清除酶表达升高相关的 ND5 变体。水蚤为研究复合体 I 组成部分的遗传变异与 ROS 生成之间的关联提供了一个独特的机会,这会影响衰老和寿命的速度。