Emaus Katlynn J, Fogo Garrett M, Wider Joseph M, Sanderson Thomas H
Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA.
Department of Emergency Medicine, University of Michigan, Ann Arbor, MI, USA.
Cell Death Dis. 2025 Jul 5;16(1):494. doi: 10.1038/s41419-025-07786-8.
Stroke and cardiac arrest claim the lives of millions worldwide each year emphasizing the importance of understanding this injury cascade. These pathologies present as a 'two hit' injury termed ischemia/reperfusion (I/R) injury. The primary injury is the initial disruption of blood flow and ischemic state while the secondary injury, paradoxically, being the return of blood flow and oxygen availability. The injury caused by reperfusion presents a viable window for therapeutic intervention, stressing the importance of understanding this injury pathology. Constantly undergoing fission and fusion, mitochondria are dynamic organelles that play a vital role in maintaining cell health and are highly susceptible to I/R injury. Following I/R injury, disrupted mitochondrial dynamics and quality control ultimately lead to a dysfunctional mitochondrial network, energy depletion and eventually cell death. While mitochondrial dynamics and quality control have been studied extensively in the realm of I/R injuries, the role of mitochondrial lipids is emerging as an important component of injury progression. The inner mitochondrial membrane lipid, cardiolipin has been demonstrated to play an integral role in maintaining mitochondrial quality control, dynamics and energy production. In response to oxidative stress, cardiolipin has been shown to interact with several important proteins involved in mitochondrial dynamics while also contributing to integral signaling cascades. This review will highlight the role of cardiolipin in mitochondrial dynamics and quality control in response to neuronal I/R injury.
中风和心脏骤停每年在全球夺走数百万人的生命，这凸显了理解这种损伤级联反应的重要性。这些病理状况表现为一种称为缺血/再灌注（I/R）损伤的“二次打击”损伤。原发性损伤是血流的初始中断和缺血状态，而矛盾的是，继发性损伤是血流和氧气供应的恢复。再灌注引起的损伤为治疗干预提供了一个可行的窗口，强调了理解这种损伤病理的重要性。线粒体不断进行裂变和融合，是动态细胞器，在维持细胞健康方面起着至关重要的作用，并且极易受到I/R损伤。I/R损伤后，线粒体动力学和质量控制的破坏最终导致线粒体网络功能失调、能量耗竭，最终导致细胞死亡。虽然线粒体动力学和质量控制在I/R损伤领域已得到广泛研究，但线粒体脂质的作用正成为损伤进展的一个重要组成部分。线粒体内膜脂质心磷脂已被证明在维持线粒体质量控制、动力学和能量产生中起着不可或缺的作用。在氧化应激反应中，心磷脂已被证明与参与线粒体动力学的几种重要蛋白质相互作用，同时也参与完整的信号级联反应。本综述将重点介绍心磷脂在神经元I/R损伤反应中线粒体动力学和质量控制中的作用。
