Department of Biology, University of Ottawa, Ottawa, ON, Canada.
Department of Biology, University of Ottawa, Ottawa, ON, Canada; University of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada.
Comp Biochem Physiol A Mol Integr Physiol. 2022 Jun;268:111185. doi: 10.1016/j.cbpa.2022.111185. Epub 2022 Mar 9.
Energetically demanding conditions such as hypoxia and exercise favour anaerobic metabolism (glycolysis), which leads to acidification of the cellular milieu from ATP hydrolysis and accumulation of the anaerobic end-product, lactate. Cellular acidification may damage mitochondrial proteins and/or alter the H gradient across the mitochondrial inner membrane, which may in turn impact mitochondrial respiration and thus aerobic ATP production. Naked mole-rats are among the most hypoxia-tolerant mammals, and putatively experience intermittent environmental and systemic hypoxia while resting and exercising in their underground burrows. Previous studies in naked mole-rat brain, heart, and skeletal muscle mitochondria have demonstrated adaptations that favour improved efficiency in hypoxic conditions; however, the impact of cellular acidification on mitochondrial function has not been explored. We hypothesized that, relative to hypoxia-intolerant mice, naked mole-rat cardiac mitochondrial respiration is less sensitive to cellular pH changes. To test this, we used high-resolution respirometry to measure mitochondrial respiration by permeabilized cardiac muscle fibres from naked mole-rats and mice exposed in vitro to a pH range from 6.6 to 7.6. Surprisingly, we found that acute pH changes do not impact cardiac mitochondrial respiration or compromise mitochondrial integrity in either species. Our results suggest that acute alterations of cellular pH have minimal impact on cardiac mitochondrial respiration.
在能量需求高的条件下，如缺氧和运动，有利于无氧代谢（糖酵解），这会导致细胞环境的酸化，因为 ATP 水解和无氧终产物乳酸的积累。细胞酸化可能会损害线粒体蛋白和/或改变线粒体内膜的 H 梯度，这可能反过来影响线粒体呼吸和有氧 ATP 的产生。裸鼹鼠是对缺氧最耐受的哺乳动物之一，在它们的地下洞穴中休息和运动时，可能会间歇性地经历环境和系统性缺氧。以前在裸鼹鼠大脑、心脏和骨骼肌线粒体中的研究表明，适应有利于改善缺氧条件下的效率；然而，细胞酸化对线粒体功能的影响尚未得到探索。我们假设，与缺氧不耐受的小鼠相比，裸鼹鼠心脏线粒体呼吸对细胞 pH 变化的敏感性较低。为了验证这一点，我们使用高分辨率呼吸计来测量体外暴露于 pH 值范围为 6.6 至 7.6 的裸鼹鼠和小鼠的通透性心肌纤维中的线粒体呼吸。令人惊讶的是，我们发现急性 pH 值变化不会影响两种物种的心脏线粒体呼吸或损害线粒体完整性。我们的结果表明，细胞 pH 值的急性变化对心脏线粒体呼吸的影响很小。
