Oxidative metabolism, ROS and NO under oxygen deprivation.

Oxygen deprivation, in line with other stress conditions, is accompanied by reactive oxygen (ROS) and nitrogen species (RNS) formation and is characterised by a set of metabolic changes collectively named as the 'oxidative stress response'. The controversial induction of oxidative metabolism under the lack of oxygen is necessitated by ROS and RNS signaling in the induction of adaptive responses, and inevitably results in oxidative damage. To prevent detrimental effects of oxidative stress, the levels of ROS and NO are tightly controlled on transcriptional, translational and metabolic levels. Hypoxia triggers the induction of genes responsible for ROS and NO handling and utilization (respiratory burst oxidase, non-symbiotic hemoglobins, several cytochromes P450, mitochondrial dehydrogenases, and antioxidant-related transcripts). The level of oxygen in the tissue is also under metabolic control via multiple mechanisms: Regulation of glycolytic and fermentation pathways to manage pyruvate availability for respiration, and adjustment of mitochondrial electron flow through NO and ROS balance. Both adaptive strategies are controlled by energy status and aim to decrease the respiratory capacity and to postpone complete anoxia. Besides local oxygen concentration, ROS and RNS formation is controlled by an array of antioxidants. Hypoxic treatment leads to the upregulation of multiple transcripts associated with ascorbate, glutathione and thioredoxin metabolism. The production of ROS and NO is an integral part of the response to oxygen deprivation which encompasses several levels of metabolic regulation to sustain redox signaling and to prevent oxidative damage.