In the first part of this review, we summarize basic mitochondrial bioenergetics concepts showing that mitochondria are critical regulators of cell life and death. Until a few decades ago, mitochondria were considered to play essential roles only in respiration, ATP formation, non-shivering thermogenesis and a variety of metabolic pathways. However, the concept presented by Peter Mitchell regarding coupling between electron flow and ATP synthesis through the intermediary of a H⁺ electrochemical potential leads to the recognition that the proton-motive force also regulates a series of relevant cell signalling processes, such as superoxide generation, redox balance and Ca²⁺ handling. Alterations in these processes lead to cell death and disease states. In the second part of this review, we discuss the role of mitochondrial dysfunctions in the specific context of hypercholesterolemia-induced atherosclerosis. We provide a literature analysis that indicates a decisive role of mitochondrial redox dysfunction in the development of atherosclerosis and discuss the underlying molecular mechanisms. Finally, we highlight the potential mitochondrial-targeted therapeutic strategies that are relevant for atherosclerosis.

在这篇综述的第一部分中，我们总结了线粒体生物能学的基本概念，表明线粒体是细胞生命和死亡的关键调节剂。直到几十年前，线粒体才被认为仅在呼吸，ATP形成，无颤抖的生热作用和各种代谢途径中起重要作用。然而，彼得·米切尔（Peter Mitchell）提出的有关通过H ⁺电化学势的中介作用在电子流与ATP合成之间进行耦合的概念导致人们认识到，质子动力还调节了一系列相关的细胞信号传导过程，例如超氧化物的产生，氧化还原平衡和Ca ²⁺处理。这些过程的改变导致细胞死亡和疾病状态。在本综述的第二部分中，我们讨论了线粒体功能障碍在高胆固醇血症诱发的动脉粥样硬化的特定情况下的作用。我们提供了表明线粒体氧化还原功能障碍在动脉粥样硬化发展中起决定性作用的文献分析，并讨论了潜在的分子机制。最后，我们重点介绍了潜在的针对动脉粥样硬化的线粒体靶向治疗策略。