Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA.
Compr Physiol. 2013 Jul;3(3):1135-90. doi: 10.1002/cphy.c120030.
Cells must continuously monitor and couple their metabolic requirements for ATP utilization with their ability to take up O2 for mitochondrial respiration. When O2 uptake and delivery move out of homeostasis, cells have elaborate and diverse sensing and response systems to compensate. In this review, we explore the biophysics of O2 and gas diffusion in the cell, how intracellular O2 is regulated, how intracellular O2 levels are sensed and how sensing systems impact mitochondrial respiration and shifts in metabolic pathways. Particular attention is paid to how O2 affects the redox state of the cell, as well as the NO, H2S, and CO concentrations. We also explore how these agents can affect various aspects of gas exchange and activate acute signaling pathways that promote survival. Two kinds of challenges to gas exchange are also discussed in detail: when insufficient O2 is available for respiration (hypoxia) and when metabolic requirements test the limits of gas exchange (exercising skeletal muscle). This review also focuses on responses to acute hypoxia in the context of the original "unifying theory of hypoxia tolerance" as expressed by Hochachka and colleagues. It includes discourse on the regulation of mitochondrial electron transport, metabolic suppression, shifts in metabolic pathways, and recruitment of cell survival pathways preventing collapse of membrane potential and nuclear apoptosis. Regarding exercise, the issues discussed relate to the O2 sensitivity of metabolic rate, O2 kinetics in exercise, and influences of available O2 on glycolysis and lactate production.
细胞必须不断监测和调节其代谢需求，以利用 ATP，并摄取 O2 用于线粒体呼吸。当 O2 的摄取和输送超出稳态时，细胞会有精细多样的感应和响应系统来进行补偿。在这篇综述中，我们探讨了 O2 和气体在细胞内扩散的生物物理学特性，细胞内 O2 是如何被调节的，细胞内 O2 水平是如何被感知的，以及感应系统如何影响线粒体呼吸和代谢途径的转变。特别关注 O2 如何影响细胞的氧化还原状态，以及 NO、H2S 和 CO 浓度。我们还探讨了这些物质如何影响气体交换的各个方面，并激活促进生存的急性信号通路。我们还详细讨论了两种对气体交换的挑战：当呼吸所需的 O2 不足时（缺氧），以及代谢需求测试气体交换的极限时（运动中的骨骼肌）。本综述还重点关注了 Hochachka 及其同事提出的原始“缺氧耐受统一理论”背景下的急性缺氧反应。它包括对线粒体电子传递、代谢抑制、代谢途径转变以及细胞存活途径的调节的讨论，这些途径可以防止膜电位崩溃和核凋亡。关于运动，讨论的问题涉及代谢率对 O2 的敏感性、运动中的 O2 动力学，以及可用 O2 对糖酵解和乳酸生成的影响。
