Hypoxia-Adaptation Involves Mitochondrial Metabolic Depression and Decreased ROS Leakage

Abstract

Through long-term laboratory selection, we have generated a Drosophila melanogaster population that tolerates severe, normally lethal, level of hypoxia. This strain lives perpetually under severe hypoxic conditions (4% O2). In order to shed light on the mechanisms involved in this adaptation, we studied the respiratory function of isolated mitochondria from the thorax of hypoxia-adapted flies (AF) using polarographic oxygen consumption while monitoring superoxide generation by electron paramagnetic resonance (EPR) techniques. AF mitochondria exhibited a significant 30% decrease in respiratory rate during state 3, while enhancing the resting respiratory rate during State 4-oligo by 220%. The activity of individual electron transport complexes I, II and III were 107%, 65%, and 120% in AF mitochondria as compared to those isolated from control flies. The sharp decrease in complex II activity and modest increase in complexes I and III resulted in >60% reduction in superoxide leakage from AF mitochondria during both NAD+-linked state 3 and State 4-oligo respirations. These results provide evidence that flies with mitochondria exhibiting decreased succinate dehydrogenase activity and reduced superoxide leakage give flies an advantage for survival in long-term hypoxia.

Abundance of Plasma Antioxidant Proteins Confers Tolerance to Acute Hypobaric Hypoxia Exposure

“…In this regard, our present results reporting abundance of antioxidant enzymes like GPx-3 and haptoglobin, which in turn maintains vascular availability of NO during several clinical disorders, provides critical insight into hypoxia tolerance. Supporting our current results, Ali et al (2012) reported that reduced superoxide leakage gives Drosophila melanogaster an advantage for survival in long-term hypoxia. These collective results highlight the crucial role of antioxidant proteins in conferring hypoxia tolerance, thereby increasing the availability of vasodilator nitric oxide into the circulation during acute altitude exposure.…”

“…The behavior, food, and water intake of these rats were similar to control (hyperventilation time 12-18 min) as well as normoxic rats. To further substantiate the hypoxia tolerance and susceptibility of rats, oxidative stress parameters such as 8-isoprostanes and protein carbonyl content were measured from plasma (Ali et al, 2012). The tolerant animals have significantly lower levels of plasma 8-isoprostane (54.53 -3.62 pg/mL, p < 0.05) and carbonyl content (116.9 -15.9 nmol/mL) as compared to control animals (76.16 -4.57 pg/mL and 152.65 -12.9 nmol/mL, respectively) and exposure control animals ( 70.27 -3.94 pg/mL and 144.28 -5.64 nmol/mL, respectively).…”

ROS-Triggered Phosphorylation of Complex II by Fgr Kinase Regulates Cellular Adaptation to Fuel Use

“…A drop in O 2 availability triggers several adaptive mechanisms, including reduction in the activities and protein levels of OXPHOS components and in ROS production (Ali et al, 2012; Heather et al, 2012; Papandreou et al, 2006), and a notable accumulation of succinate (Cascarano et al, 1976). However, sudden reoxygenation, as occurs in reperfusion after ischemia, is accompanied by a sharp increase in ROS production as the electron transport chain readapts to oxygen availability.…”

Metabolic readjustment in juvenile South African abalone (Haliotis midae) acclimated to combinations of temperature and dissolved oxygen levels

“…Mitochondria respond rapidly to oxygen availability and this affects their functional state, which in turn affects ATP availability (Ali et al, 2012), and cells need to adjust their metabolism accordingly. Cytochrome c oxidase (cox) is a mitochondrial enzyme complex that catalyses the transfer of electrons from reduced cytochrome c to molecular oxygen in the final step of respiration.…”