Higher NDUFS8 Serum Levels Correlate with Better Insulin Sensitivity in Type 1 Diabetes

Aim: The aim of the study was to evaluate the function of Complex I by measuring NADH dehydrogenase [ubiquinone] iron-sulfur protein 8 serum level and the relationship with insulin resistance in type 1 diabetes. T1DM causes adverse changes in the mitochondria, which can influence the development of chronic complications. The NADH dehydrogenase [ubiquinone] iron-sulfur protein 8 (NDUFS8 protein) is a subunit of NADH dehydrogenase and plays an important role in the mitochondrial function. NDUFS8 serum concentration probably reflects the function of mitochondria. Methods: All of 36 people suffer from T1DM. All participants were treated with functional intensive insulin therapy. NDUFS8 protein serum concentration was measured using the ELISA test. Insulin resistance was evaluated with indirect marker estimated glucose disposal rate (eGDR). The group was divided on the base of median value of eGDR (higher eGDR – less IR). Results: The study group consisted of 12 women and 24 men, aged 39.5 (28.0-46.5) years with the duration of the disease 22 (15-26) years. Medians of eGDR and NDUFS8 protein concentration were 7.6 (5.58-8.99) mg/kg/min and 2.25 (0.72-3.81) ng/ml, respectively. The group with higher insulin sensitivity had higher NDUFS8 protein serum concentration, lower WHR, BMI and they were younger. A negative correlation was observed between NDUFS8 protein serum concentration and WHR (rs=-0.35,p=0.03), whereas a positive correlation was observed between NDUFS8 protein serum concentration and eGDR (rs=0.43,p=0.008). Multivariate linear regression confirmed a significant association between insulin sensitivity and better mitochondrial function (beta=0.54,p=0.003), independent of age, duration of diabetes and smoking. Conclusions: Higher NDUFS8 protein serum concentration is associated with higher insulin sensitivity among people with T1DM and might reflects better mitochondrial function.

A Model of Aerobic and Anaerobic Metabolism of Hydrogen in the Extremophile Acidithiobacillus ferrooxidans

Hydrogen can serve as an electron donor for chemolithotrophic acidophiles, especially in the deep terrestrial subsurface and geothermal ecosystems. Nevertheless, the current knowledge of hydrogen utilization by mesophilic acidophiles is minimal. A multi-omics analysis was applied on Acidithiobacillus ferrooxidans growing on hydrogen, and a respiratory model was proposed. In the model, [NiFe] hydrogenases oxidize hydrogen to two protons and two electrons. The electrons are used to reduce membrane-soluble ubiquinone to ubiquinol. Genetically associated iron-sulfur proteins mediate electron relay from the hydrogenases to the ubiquinone pool. Under aerobic conditions, reduced ubiquinol transfers electrons to either cytochrome aa3 oxidase via cytochrome bc1 complex and cytochrome c4 or the alternate directly to cytochrome bd oxidase, resulting in proton efflux and reduction of oxygen. Under anaerobic conditions, reduced ubiquinol transfers electrons to outer membrane cytochrome c (ferrireductase) via cytochrome bc1 complex and a cascade of electron transporters (cytochrome c4, cytochrome c552, rusticyanin, and high potential iron-sulfur protein), resulting in proton efflux and reduction of ferric iron. The proton gradient generated by hydrogen oxidation maintains the membrane potential and allows the generation of ATP and NADH. These results further clarify the role of extremophiles in biogeochemical processes and their impact on the composition of the deep terrestrial subsurface.