Mar 1
Chemistry Department Seminar: David Hanna - POSTPONED to SPRING 2024
"H2S preconditioning induces long-lived perturbations in O2 metabolism"
Mitochondria house the electron transport chain (ETC), a chain of complexes required for generating a proton gradient used by cells to facilitate ATP synthesis. Hydrogen sulfide is a respiratory substrate of ETC at low concentrations, stimulating O2 consumption and ATP synthesis, but is a potent respiratory inhibitor at high concentrations. For these reasons, cells maintain low steady-state levels of H2S, and prevent its accumulation via clearance by the mitochondrial sulfide oxidation pathway. However, certain cellular stresses, changes in diet, or gut microbial composition can elevate cellular sulfide levels to transiently inhibit cellular respiration. Our data supports a model by which sulfide competitively inhibits cellular respiration by binding to an iron center of Complex IV at low-moderate concentrations, which is fully reversible. However, at higher concentrations sulfide inhibit Complex IV by binding to both iron and copper metal centers, causing long lasting changes in the ability of cells to utilize O2, rewiring cells to a hypometabolic state.
*This seminar counts towards the chemistry major seminar attendance requirement.