Department of Biology, McMaster University, Hamilton, ON, Canada.
Division of Biological Sciences, University of Montana, Missoula, MT, USA.
J Physiol. 2020 Dec;598(23):5411-5426. doi: 10.1113/JP280298. Epub 2020 Sep 14.
Small mammals native to high altitude must sustain high rates of thermogenesis to cope with cold. Skeletal muscle is a key site of shivering and non-shivering thermogenesis, but the importance of mitochondrial plasticity in cold hypoxic environments remains unresolved. We examined high-altitude deer mice, which have evolved a high capacity for aerobic thermogenesis, to determine the mechanisms of mitochondrial plasticity during chronic exposure to cold and hypoxia, alone and in combination. Cold exposure in normoxia or hypoxia increased mitochondrial leak respiration and decreased phosphorylation efficiency and OXPHOS coupling efficiency, which may serve to augment non-shivering thermogenesis. Cold also increased muscle oxidative capacity, but reduced the capacity for mitochondrial respiration via complex II relative to complexes I and II combined. High-altitude mice had a more oxidative muscle phenotype than low-altitude mice. Therefore, both plasticity and evolved changes in muscle mitochondria contribute to thermogenesis at high altitude.
Small mammals native to high altitude must sustain high rates of thermogenesis to cope with cold and hypoxic environments. Skeletal muscle is a key site of shivering and non-shivering thermogenesis, but the importance of mitochondrial plasticity in small mammals at high altitude remains unresolved. High-altitude deer mice (Peromyscus maniculatus) and low-altitude white-footed mice (P. leucopus) were born and raised in captivity, and chronically exposed as adults to warm (25°C) normoxia, warm hypoxia (12 kPa O ), cold (5°C) normoxia, or cold hypoxia. We then measured oxidative enzyme activities, oxidative fibre density and capillarity in the gastrocnemius, and used a comprehensive substrate titration protocol to examine the function of muscle mitochondria by high-resolution respirometry. Exposure to cold in both normoxia or hypoxia increased the activities of citrate synthase and cytochrome oxidase. In lowlanders, this was associated with increases in capillary density and the proportional abundance of oxidative muscle fibres, but in highlanders, these traits were unchanged at high levels across environments. Environment had some distinct effects on mitochondrial OXPHOS capacity between species, but the capacity of complex II relative to the combined capacity of complexes I and II was consistently reduced in both cold environments. Both cold environments also increased leak respiration and decreased phosphorylation efficiency and OXPHOS coupling efficiency in both species, which may serve to augment non-shivering thermogenesis. These cold-induced changes in mitochondrial function were overlaid upon the generally more oxidative phenotype of highlanders. Therefore, both plasticity and evolved changes in muscle mitochondria contribute to thermogenesis at high altitudes.
原产于高海拔地区的小型哺乳动物必须维持较高的产热率以应对寒冷。骨骼肌是寒战和非寒战产热的关键部位，但线粒体可塑性在寒冷低氧环境中的重要性仍未得到解决。我们研究了高海拔鹿鼠，它们已经进化出了高能力的有氧产热能力，以确定在单独和组合的慢性冷暴露和低氧暴露下线粒体可塑性的机制。常氧或低氧冷暴露增加了线粒体漏呼吸，并降低了磷酸化效率和氧化磷酸化偶联效率，这可能有助于增加非寒战产热。冷暴露还增加了肌肉氧化能力，但通过相对于复合物 I 和 II 复合物降低了肌肉中线粒体呼吸的能力。高海拔小鼠的肌肉表现出比低海拔小鼠更氧化的表型。因此，肌肉线粒体的可塑性和进化变化都有助于高海拔地区的产热。
原产于高海拔地区的小型哺乳动物必须维持较高的产热率以应对寒冷和低氧环境。骨骼肌是寒战和非寒战产热的关键部位，但线粒体可塑性在高海拔地区的小型哺乳动物中的重要性仍未得到解决。高山鹿鼠（Peromyscus maniculatus）和低地白足鼠（P. leucopus）在圈养中出生和长大，并在成年后长期暴露于温暖（25°C）常氧、温暖低氧（12kPa O 2 ）、寒冷（5°C）常氧或寒冷低氧环境中。然后，我们测量了比目鱼肌中的氧化酶活性、氧化纤维密度和毛细血管密度，并使用综合底物滴定方案通过高分辨率呼吸测定法检查肌肉线粒体的功能。常氧或低氧冷暴露均增加了柠檬酸合酶和细胞色素氧化酶的活性。在低地动物中，这与毛细血管密度和氧化肌纤维的比例增加有关，但在高地动物中，这些特征在不同环境下始终保持高水平不变。环境对物种间的线粒体氧化磷酸化能力有一些独特的影响，但在两种冷环境中，复合物 II 的能力相对于复合物 I 和 II 的组合能力始终降低。两种冷环境还增加了漏呼吸，并降低了磷酸化效率和氧化磷酸化偶联效率，这可能有助于增加非寒战产热。线粒体功能的这些冷诱导变化叠加在高地动物通常更氧化的表型上。因此，肌肉线粒体的可塑性和进化变化都有助于高海拔地区的产热。
