A paradigm shift in oxygen sensing with a twist in the tale!

Abstract

AMP-activated protein kinase (AMPK) is pivotal to metabolic homeostasis in eukaryotes, serving as a critical energy sensor. Increased AMPK activity during oxygen deprivation (hypoxia) protects against potentially catastrophic deficits in ATP supply. Whilst the nervous system circuitry for elaboration of the complex cardiorespiratory response to hypoxia has been understood in some detail for many decades, there is continued and considerable interest in the molecular machinery underpinning the mechanism(s) of oxygen sensing. In this issue of the Biochemical Journal, Evans et al. (2016) review their recent work, which points to a pivotal role for AMPK in the transduction of cellular hypoxic stress to integrated ventilatory behaviour, critical in the defence of whole-body oxygen homeostasis. Of great surprise, there is profound blunting of the hyperventilatory response to hypoxic stress in AMPK deficient mice, with resultant dysregulated breathing arising in spite of normal peripheral oxygen sensing and appropriate sensory input to the brain! Their pointedly provocative review challenges current dogma, and in doing so raises intriguing questions that probe fundamental aspects of our understanding of the mammalian ventilatory response to hypoxic stress. The engaging review by Evans et al. (2016) is an interesting read that is sure to encourage colourful debate

Extended hypoxia‐mediated H2S production provides for long‐term oxygen sensing

“…Historically, a variety of acute and chronic O 2 ‐sensing mechanisms have been proposed. These include increases, or paradoxically decreases, in reactive oxygen species (ROS), activation or inactivation of metabolites, for example, nitric oxide, prostanoids, etc, AMP‐activated protein kinase, ion channels, Na,K ATPase, haeme and other proteins and the hypoxia inducible factors …”

RNA SEQ Analysis Indicates that the AE3 Cl−/HCO3 − Exchanger Contributes to Active Transport-Mediated CO2 Disposal in Heart

“…The expression of both Ppard and Pparg are reduced by hypoxia 66 , 67 , consistent with a role for AE3 in maintenance of O 2 /CO 2 balance. Prkag2 and Prkab1 , regulatory subunits of AMPK, which plays a major role in energy sensing, energy metabolism 68 , and response to hypoxia 69 , were up-regulated. Ppip5k2 (diphosphoinositol pentakisphosphate kinase 2, 1.38-fold increase, not shown) regulates inositol pyrophosphate metabolism and is an AMPK-independent energy sensor and regulator 70 .…”