Univ-Lyon, CarMeN Laboratory, Inserm U1060, Université Claude Bernard Lyon 1, INSA Lyon, F-69550 Bron, France.
Hospices Civils de Lyon, Groupement Hospitalier EST, Département de Cardiologie, IHU-OPERA Bâtiment B13, F-69500 Bron, France.
Cells. 2022 Mar 14;11(6):989. doi: 10.3390/cells11060989.
Hypothermia provides an effective neuro and cardio-protection in clinical settings implying ischemia/reperfusion injury (I/R). At the onset of reperfusion, succinate-induced reactive oxygen species (ROS) production, impaired oxidative phosphorylation (OXPHOS), and decreased Ca retention capacity (CRC) concur to mitochondrial damages. We explored the effects of temperature from 6 to 37 °C on OXPHOS, ROS production, and CRC, using isolated mitochondria from mouse brain and heart. Oxygen consumption and ROS production was gradually inhibited when cooling from 37 to 6 °C in brain mitochondria (BM) and heart mitochondria (HM). The decrease in ROS production was gradual in BM but steeper between 31 and 20 °C in HM. In respiring mitochondria, the gradual activation of complex II, in addition of complex I, dramatically enhanced ROS production at all temperatures without modifying respiration, likely because of ubiquinone over-reduction. Finally, CRC values were linearly increased by cooling in both BM and HM. In BM, the Ca uptake rate by the mitochondrial calcium uniporter (MCU) decreased by 2.7-fold between 25 and 37 °C, but decreased by 5.7-fold between 25 and 37 °C in HM. In conclusion, mild cold (25-37 °C) exerts differential inhibitory effects by preventing ROS production, by reverse electron transfer (RET) in BM, and by reducing MCU-mediated Ca uptake rate in BM and HM.
在临床环境中，低温提供了有效的神经和心脏保护作用，暗示缺血/再灌注损伤（I/R）。在再灌注开始时，琥珀酸盐诱导的活性氧（ROS）产生、氧化磷酸化（OXPHOS）受损和 Ca 保留能力（CRC）下降共同导致线粒体损伤。我们使用来自小鼠大脑和心脏的分离线粒体，探索了从 6 到 37°C 的温度对 OXPHOS、ROS 产生和 CRC 的影响。在大脑线粒体（BM）和心脏线粒体（HM）中，从 37°C 冷却到 6°C 时，耗氧量和 ROS 产生逐渐受到抑制。在 BM 中，ROS 产生的减少是逐渐的，但在 HM 中，从 31°C 到 20°C 时，减少更为陡峭。在呼吸的线粒体中，除了复合体 I 之外，复合体 II 的逐渐激活极大地增强了所有温度下的 ROS 产生，而不改变呼吸，可能是由于泛醌过度还原。最后，在 BM 和 HM 中，冷却均使 CRC 值呈线性增加。在 BM 中，线粒体钙单向转运蛋白（MCU）的 Ca 摄取速率在 25-37°C 之间降低了 2.7 倍，但在 HM 中，该速率在 25-37°C 之间降低了 5.7 倍。总之，轻度寒冷（25-37°C）通过在 BM 中防止 ROS 产生、通过逆向电子传递（RET）以及通过降低 BM 和 HM 中 MCU 介导的 Ca 摄取速率来产生差异抑制效应。
