Tessa Perez
Research Mentor: Ruma Banerjee
Mentor Department: Biological Chemistry, Medicine
Author(s): Tessa Perez, Roshan Kumar
Session: Session 5 (2:00 PM – 2:50 PM)
Presentation Type: Poster 57
Abstract
Hydrogen sulfide (H2S) is a redox active signaling metabolite produced by the metabolic activity of both host and gut microbial cells. At low levels, H2S supports energy metabolism by enhancing ATP generation, whereas at high levels, it is a respiratory poison that inhibits mitochondrial complex IV. Cellular H2S homeostasis is maintained through a balance between its synthesis and its removal via the mitochondrial oxidation pathway. Activity of sulfide quinone oxidoreductase (SQOR) initiates H2S oxidation and concomitantly transfers electrons to coenzyme Q, thereby linking sulfide oxidation to the mitochondrial electron transport chain. When H2S accumulates due to increased production or decreased clearance, it impacts cellular processes and shifts the intracellular redox balance toward a more reduced state. Elevated H2S levels have been implicated in several pathological conditions, including ulcerative colitis, inflammatory bowel disease, colon cancer, and Leigh syndrome. However, mechanistic insights into how H2S contributes to gut and brain pathologies remain limited, largely due to the absence of a reliable model system to modulate H2S levels in vivo. To address this gap, we have developed an intestine-specific SQOR knockout (KO) mouse model that serves as a powerful tool to investigate the link between gut H2S elevation and disease. We are also examining the local and long-range effects of a methionine-rich diet (MRD) in control versus SQOR KO mice. Interestingly, female SQOR KO mice display decreased exploratory locomotory behavior compared with male SQOR KO mice on a 1.5% MRD. We also found that colon epithelial cells from male SQOR KO mice express lower levels of ?-cystathionase, an enzyme involved in H2S production. Our finding suggests that male SQOR KO mice might compensate for impaired H2S clearance by decreasing endogenous H2S synthesis. Next, the effects of genotype and diet on ?-cystathionase mice will be investigated separately and our results will be discussed.
