Department of Biosciences, Section for Physiology and Cellular Biology, University of Oslo, Oslo, Norway.
Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Acta Physiol (Oxf). 2024 Dec;240(12):e14244. doi: 10.1111/apha.14244. Epub 2024 Oct 28.
In most vertebrates, oxygen deprivation and subsequent re-oxygenation are associated with mitochondrial impairment and excess production of reactive oxygen species (ROS) like hydrogen peroxide (HO). This in turn triggers a cascade of cell-damaging events in a temperature-dependent manner. The crucian carp (Carassius carassius) is one of few vertebrates that survives months without oxygen at cold temperatures and overcomes oxidative damage during re-oxygenation periods. Mitochondria of this anoxia-tolerant species therefore serve as an excellent model in translational research to study adaptation and resilience to low oxygen conditions and thermal variability.
Here, we used high-resolution respirometry on isolated mitochondria from hearts of crucian carp and the anoxia-intolerant mouse (Mus musculus), at 37 and 8°C; two temperatures relevant for transplantation medicine (i.e., graft preservation and subsequent rewarming).
We find: (1) a striking difference in HO release between the two species at 37°C despite comparable mitochondrial efficiency and capacity, (2) a massive HO release after inhibition of complex V in mouse at 37°C that is absent in crucian carp, and prevented in mouse by incubation at 8°C or uncoupling with a protonophore at 37°C, and (3) indications that differences in mitochondrial complex I and II capacity and thermal sensitivity influence the release of mitochondrial HO relative to respiration.
Our findings provide comparative insights into a spectrum of mitochondrial adaptations in vertebrates and the importance of thermal variability. Furthermore, the species- and temperature-related changes associated with mitochondria highlighted in this study may help identify mitochondria-based targets for translational medicine.
在大多数脊椎动物中，缺氧及其随后的复氧与线粒体损伤和活性氧（ROS）的过度产生有关，如过氧化氢（HO）。这反过来又以温度依赖的方式引发一连串的细胞损伤事件。鲤鱼（Carassius carassius）是少数几种在低温下几个月无需氧气就能存活并在复氧期间克服氧化损伤的脊椎动物之一。因此，这种耐缺氧物种的线粒体是研究适应和抵御低氧条件和温度变化的转化研究中的一个极好模型。
在这里，我们在 37 和 8°C 下使用来自鲤鱼和不耐缺氧的小鼠（Mus musculus）心脏的分离线粒体进行高分辨率呼吸测定；这两个温度与移植医学相关（即移植物保存和随后复温）。
我们发现：（1）尽管线粒体效率和容量相当，但两种物种在 37°C 时的 HO 释放存在显著差异，（2）在 37°C 下抑制复合物 V 后，小鼠中会大量释放 HO，但在鲤鱼中不存在，并且在 8°C 下孵育或在 37°C 下用质子载体解偶联可以防止小鼠中出现这种情况，（3）表明线粒体复合物 I 和 II 能力和热敏感性的差异会影响与呼吸相比，线粒体 HO 的释放。
我们的发现为脊椎动物中线粒体适应的一系列比较提供了深入的了解，并强调了热变异性的重要性。此外，本研究中强调的与物种和温度相关的与线粒体相关的变化可能有助于确定基于线粒体的转化医学目标。
