Energy Conservation and Carbon Flux Distribution During Fermentation of CO or H2/CO2 by Clostridium ljungdahlii.

Both CO and H2 can be utilized as energy sources during the autotrophic growth of Clostridium ljungdahlii. In principle, CO is a more energetically and thermodynamically favorable energy source for gas fermentation in comparison to H2. Therefore, metabolism may vary during growth under different energy sources. In this study, C. ljungdahlii was fed with CO and/or CO2/H2 at pH 6.0 with a gas pressure of 0.1 MPa. C. ljungdahlii primarily produced acetate in the presence of H2 as an energy source, but produced alcohols with CO as an energy source under the same fermentation conditions. A key enzyme activity assay, metabolic flux analysis, and comparative transcriptomics were performed for investigating the response mechanism of C. ljungdahlii under different energy sources. A CO dehydrogenase and an aldehyde:ferredoxin oxidoreductase were found to play important roles in CO utilization and alcohol production. Based on these findings, novel metabolic schemes are proposed for C. ljungdahlii growing on CO and/or CO2/H2. These schemes indicate that more ATP is produced during CO-fermentation than during H2-fermentation, leading to increased alcohol production.

Corticosterone induces neurotoxicity in PC12 cells via disrupting autophagy flux mediated by AMPK/mTOR signaling.

AIMS: Our previous study indicated that chronic stress caused autophagy impairment and subsequent neuron apoptosis in hippocampus. However, the mechanism underlying the stress-induced damage to neurons is unclear. In present work, we investigated whether stress-level glucocorticoids (GCs) GCs promoted PC12 cell damage via AMPK/mTOR signaling-mediated autophagy. METHODS: Chronic stress-induced PC12 cell injury model was built by treatment with high level corticosterone (CORT). Cell injury was evaluated by flow cytometry assay and transmission electron microscopy observation. RESULTS: Autophagy flux was measured based on the changes in LC3-II and P62 protein expressions, and the color alteration of mCherry-GFP-LC3-II transfection. Our results showed that CORT not only increased cell injury and apoptosis, but also dysregulated AMPK/mTOR signaling-mediated autophagy flux, as indicated by the upregulated expression of LC3-II and P62 proteins, and the lowered ration of autolysosomes to autophagosomes. Mechanistically, our results demonstrated that autophagy activation by AMPK activator metformin or mTOR inhibitor rapamycin obviously promotes cell survival and autophagy flux, improved mitochondrial ultrastructure, and reduced expression of Cyt-C and caspase-3 in CORT-induced PC12 cells. CONCLUSION: These results indicate that high CORT triggers PC12 cell damage through disrupting AMPK/mTOR-mediated autophagy flux. Targeting this signaling may be a promising approach to protect against high CORT and chronic stress-induced neuronal impairment.