Kuznetsov Andrey V, Javadov Sabzali, Margreiter Raimund, Grimm Michael, Hagenbuchner Judith, Ausserlechner Michael J
Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Medical University of Innsbruck, Innsbruck A-6020, Austria.
Department of Pediatrics I, Medical University of Innsbruck, Innsbruck A-6020, Austria.
Antioxidants (Basel). 2019 Oct 6;8(10):454. doi: 10.3390/antiox8100454.
Mitochondria play a critical role in maintaining cellular function by ATP production. They are also a source of reactive oxygen species (ROS) and proapoptotic factors. The role of mitochondria has been established in many aspects of cell physiology/pathophysiology, including cell signaling. Mitochondria may deteriorate under various pathological conditions, including ischemia-reperfusion (IR) injury. Mitochondrial injury can be one of the main causes for cardiac and other tissue injuries by energy stress and overproduction of toxic reactive oxygen species, leading to oxidative stress, elevated calcium and apoptotic and necrotic cell death. However, the interplay among these processes in normal and pathological conditions is still poorly understood. Mitochondria play a critical role in cardiac IR injury, where they are directly involved in several pathophysiological mechanisms. We also discuss the role of mitochondria in the context of mitochondrial dynamics, specializations and heterogeneity. Also, we wanted to stress the existence of morphologically and functionally different mitochondrial subpopulations in the heart that may have different sensitivities to diseases and IR injury. Therefore, various cardioprotective interventions that modulate mitochondrial stability, dynamics and turnover, including various pharmacologic agents, specific mitochondrial antioxidants and uncouplers, and ischemic preconditioning can be considered as the main strategies to protect mitochondrial and cardiovascular function and thus enhance longevity.
线粒体通过产生三磷酸腺苷(ATP)在维持细胞功能方面发挥着关键作用。它们也是活性氧(ROS)和促凋亡因子的来源。线粒体的作用已在细胞生理/病理生理的许多方面得到证实,包括细胞信号传导。在包括缺血再灌注(IR)损伤在内的各种病理条件下,线粒体可能会恶化。线粒体损伤可能是心脏和其他组织因能量应激和有毒活性氧过度产生而受损的主要原因之一,导致氧化应激、钙升高以及细胞凋亡和坏死性死亡。然而,在正常和病理条件下,这些过程之间的相互作用仍知之甚少。线粒体在心脏IR损伤中起关键作用,它们直接参与多种病理生理机制。我们还讨论了线粒体在细胞动力学、特化和异质性背景下的作用。此外,我们想强调心脏中形态和功能不同的线粒体亚群的存在,这些亚群可能对疾病和IR损伤具有不同的敏感性。因此,各种调节线粒体稳定性、动力学和更新的心脏保护干预措施,包括各种药物、特定的线粒体抗氧化剂和解偶联剂,以及缺血预处理,可以被视为保护线粒体和心血管功能从而延长寿命的主要策略。