Liver mitochondrial respiratory plasticity and oxygen uptake evoked by cobalt chloride in rats with low and high resistance to extreme hypobaric hypoxia

High-altitude intolerance and consequently high-altitude sickness, is difficult to predict. Liver is an essential organ in glucose and lipid metabolism, and may play key role in the adaptation to high altitude. In response to extreme high altitude, mitochondrial respiration exhibits changes in substrate metabolism, mitochondrial electron transport chain activity, and respiratory coupling. We determined the cobalt chloride (CoCl2) effects on liver mitochondrial plasticity and oxygen uptake in rats with low resistance (LR) and high resistance (HR) to extreme hypobaric hypoxia. The polarographic method proposed by Chance and Williams was used as a simple and effective tool to trace mitochondrial functionality and oxygen consumption. HR rats had more efficient processes of NADH- and FAD-generated mitochondrial oxidation. CoCl2 promoted more efficient NADH-generated and diminished less efficient FAD-generated mitochondrial respiratory reactions in HR rats. CoCl2 diminished both aerobic and anaerobic processes in LR rats. Glutamate and pyruvate substrates of NADH-generated mitochondrial pathways were highly affected by CoCl2. Red blood cells acted as cobalt depots in HR and LR rats. We have unveiled several mechanisms leading to differentiated mitochondrial respiratory responses to hypobaric hypoxia in LR and HR rats. Our study strongly supports the existence of adaptive liver mitochondrial plasticity to extreme hypoxia.

Respiratory heterogeneity shapes biofilm formation and host colonization in uropathogenic Escherichia coli

Biofilms are multicellular bacterial communities encased in a self-secreted extracellular matrix comprised of polysaccharides, proteinaceous fibers, and DNA. Organization of these components lends spatial organization to the biofilm community such that biofilm residents can benefit from the production of common goods, while being protected from exogenous insults. Spatial organization is driven by the presence of chemical gradients, such as oxygen. Here we quantified and localized the expression of two Escherichia coli cytochrome oxidases in cells found in the biofilm state and defined their contribution to biofilm architecture. These studies elucidated a role for the high-affinity quinol oxidase cytochrome bd in matrix production and biofilm resident protection. Cytochrome bd was the most abundantly expressed respiratory complex in the biofilm community and was localized in the biofilm interior. Depletion of the cytochrome bd-expressing subpopulation led to decreased extracellular matrix and increased sensitivity of the community to exogenous stresses. Interrogation of the distribution of cytochrome oxidases in the planktonic state revealed that ∼15% of the population expresses cytochrome bd at atmospheric oxygen concentration, and this population dominates during acute urinary tract infection. These data point towards a bet-hedging mechanism in which heterogeneous expression of respiratory complexes ensures respiratory plasticity of E. coli across diverse host niches.