Regulation of Cellular Gas Exchange, Oxygen Sensing, and Metabolic Control
- 1 July 2013
- book chapter
- review article
- Published by Wiley in Comprehensive Physiology
- Vol. 3 (3), 1135-1190
- https://doi.org/10.1002/cphy.c120030
Abstract
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. © 2013 American Physiological Society. Compr Physiol 3:1135‐1190, 2013.Keywords
This publication has 101 references indexed in Scilit:
- The carbon monoxide donor, CORM-2, is an antagonist of ATP-gated, human P2X4 receptorsPurinergic Signalling, 2011
- Regulation of mitochondrial fission by intracellular Ca2+ in rat ventricular myocytesBiochimica et Biophysica Acta (BBA) - Bioenergetics, 2010
- The role of Ca2+ signaling in the coordination of mitochondrial ATP production with cardiac workBiochimica et Biophysica Acta (BBA) - Bioenergetics, 2009
- 110 Years of the Meyer–Overton Rule: Predicting Membrane Permeability of Gases and Other Small CompoundsChemphyschem, 2009
- Kinetics of nucleotide binding to the β-subunit (AKR6A2) of the voltage-gated potassium (Kv) channelChemico-Biological Interactions, 2009
- Nitrite as regulator of hypoxic signaling in mammalian physiologyMedicinal Research Reviews, 2009
- Induction of HIF‐1α expression by intermittent hypoxia: Involvement of NADPH oxidase, Ca2+ signaling, prolyl hydroxylases, and mTORJournal of Cellular Physiology, 2008
- Protein kinase C as a stress sensorCellular Signalling, 2007
- Site specific phosphorylation of cytochrome c oxidase subunits I, IVi1 and Vb in rabbit hearts subjected to ischemia/reperfusionFEBS Letters, 2007
- AMP‐activated protein kinase mediates preconditioning in cardiomyocytes by regulating activity and trafficking of sarcolemmal ATP‐sensitive K+ channelsJournal of Cellular Physiology, 2006