Sulfide Quinone Oxidoreductase Alleviates Acute Ulcerative Colitis by Regulating Mitochondrial Dysfunction

Area of Science:

• Mitochondrial Biology
• Gastroenterology
• Cellular Metabolism

Background:

• Mitochondrial dysfunction is linked to inflammatory bowel disease (IBD) progression.
• Sulfide quinone oxidoreductase (SQOR) is a key enzyme in mitochondrial sulfide metabolism.
• SQOR downregulation was observed in colitis models.

Purpose of the Study:

• To investigate the role of SQOR in intestinal epithelial cells during colitis.
• To elucidate the mechanisms by which SQOR deficiency impacts mitochondrial function and epithelial barrier integrity.
• To explore SQOR's potential as a therapeutic target for ulcerative colitis (UC).

Main Methods:

• Generated intestinal epithelial cell-specific SQOR knockout (Sqor CKO) mice.
• Induced acute ulcerative colitis using Dextran Sodium Sulfate (DSS) in wild-type and Sqor CKO mice.
• Analyzed mitochondrial morphology, function, epithelial barrier integrity, and oxidative stress markers (e.g., MDA, ROS).
• Assessed the impact of ROS scavengers (NAC) on colitis severity.

Main Results:

• Sqor CKO mice exhibited increased susceptibility to DSS-induced colitis with reduced hydrogen sulfide (H2S) levels.
• SQOR deficiency led to epithelial barrier breakdown via tight junction protein disruption.
• Mitochondrial damage, increased lipid peroxidation, malondialdehyde (MDA), and ferroptosis were observed in Sqor CKO mice.
• SQOR regulates mitochondrial dynamics and reactive oxygen species (ROS) levels.
• NAC treatment ameliorated colitis symptoms in DSS-treated Sqor CKO mice.

Conclusions:

• SQOR plays a critical protective role in intestinal epithelial cells during colitis.
• SQOR maintains mitochondrial homeostasis by regulating ROS and preventing ferroptosis.
• Targeting SQOR may offer a novel therapeutic strategy for ulcerative colitis.