研究揭示线粒体呼吸体水平极度降低的小鼠中呼吸链能力和生理机能的保留

来源:科学网 发布时间:2023年08月31日 浏览次数: 【字体: 收藏 打印文章

瑞典卡洛琳卡学院Nils-Gran Larsson等研究人员合作揭示线粒体呼吸体水平极度降低的小鼠中呼吸链能力和生理机能的保留。2023年8月25日,《细胞—代谢》杂志在线发表了这项成果。

研究人员表示哺乳动物呼吸链复合物I、III2和IV(CI、CIII2和CIV)对细胞的生物能至关重要,它们形成了一个稳定的集合体——呼吸体(CI-CIII2-CIV),在生物化学和结构上都有详细的报道。呼吸体在生物能和新陈代谢调控中的作用引起了激烈的争论,而且由于单个呼吸链复合物与高水平的呼吸体共存,因此很难对其进行研究。

为了深入研究呼吸体在体内的作用,研究人员产生了呼吸链复合物水平正常但呼吸体水平严重下降的纯合敲除小鼠。令人惊讶的是,这种突变小鼠非常健康,呼吸链能力得以保留,且运动表现正常。这些研究结果表明,高水平的呼吸体对于维持小鼠的生物能和生理机能是可有可无的,但同时也提出了关于呼吸体的其他功能的问题,例如与调节蛋白质稳定性和防止与年龄相关的蛋白质聚集有关的功能。

附:英文原文

Title: Preserved respiratory chain capacity and physiology in mice with profoundly reduced levels of mitochondrial respirasomes

Author: Dusanka Milenkovic, Jelena Misic, Johannes F. Hevler, Thibaut Molinié, Injae Chung, Ilian Atanassov, Xinping Li, Roberta Filograna, Andrea Mesaros, Arnaud Mourier, Albert J.R. Heck, Judy Hirst, Nils-Gran Larsson

Issue&Volume: 2023-08-25

Abstract: The mammalian respiratory chain complexes I, III2, and IV (CI, CIII2, and CIV) are critical for cellular bioenergetics and form a stable assembly, the respirasome (CI-CIII2-CIV), that is biochemically and structurally well documented. The role of the respirasome in bioenergetics and the regulation of metabolism is subject to intense debate and is difficult to study because the individual respiratory chain complexes coexist together with high levels of respirasomes. To critically investigate the in vivo role of the respirasome, we generated homozygous knockin mice that have normal levels of respiratory chain complexes but profoundly decreased levels of respirasomes. Surprisingly, the mutant mice are healthy, with preserved respiratory chain capacity and normal exercise performance. Our findings show that high levels of respirasomes are dispensable for maintaining bioenergetics and physiology in mice but raise questions about their alternate functions, such as those relating to the regulation of protein stability and prevention of age-associated protein aggregation.

DOI: 10.1016/j.cmet.2023.07.015

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00289-9

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