Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism

HIF prolyl hydroxylases (PHD1-3) are oxygen sensors that regulate the stability of the hypoxia-inducible factors (HIFs) in an oxygen-dependent manner. Here, we show that loss of Phd1 lowers oxygen consumption in skeletal muscle by reprogramming glucose metabolism from oxidative to more anaerobic ATP production through activation of a Pparalpha pathway. This metabolic adaptation to oxygen conservation impairs oxidative muscle performance in healthy conditions, but it provides acute protection of myofibers against lethal ischemia. Hypoxia tolerance is not due to HIF-dependent angiogenesis, erythropoiesis or vasodilation, but rather to reduced generation of oxidative stress, which allows Phd1-deficient myofibers to preserve mitochondrial respiration. Hypoxia tolerance relies primarily on Hif-2alpha and was not observed in heterozygous Phd2-deficient or homozygous Phd3-deficient mice. Of medical importance, conditional knockdown of Phd1 also rapidly induces hypoxia tolerance. These findings delineate a new role of Phd1 in hypoxia tolerance and offer new treatment perspectives for disorders characterized by oxidative stress.     

Winter cold of eastern continental boundaries induced by warm ocean waters

In winter, northeastern North America and northeastern Asia are both colder than other regions at similar latitudes. This has been attributed to the effects of stationary weather systems set by elevated terrain (orography), and to a lack of maritime influences from the prevailing westerly winds. However, the differences in extent and orography between the two continents suggest that further mechanisms are involved. Here we show that this anomalous winter cold can result in part from westward radiation of large-scale atmospheric waves--nearly stationary Rossby waves--generated by heating of the atmosphere over warm ocean waters. We demonstrate this mechanism using simulations with an idealized general circulation model, with which we show that the extent of the cold region is controlled by properties of Rossby waves, such as their group velocity and its dependence on the planetary rotation rate. Our results show that warm ocean waters contribute to the contrast in mid-latitude winter temperatures between eastern and western continental boundaries not only by warming western boundaries, but also by cooling eastern boundaries.