CKMT1 deficiency contributes to mitochondrial dysfunction and promotes intestinal epithelial cell apoptosis via...

Area of Science:

• Molecular Biology
• Gastroenterology
• Mitochondrial Biology

Background:

• Mitochondrial dysfunction is implicated in ulcerative colitis (UC) pathogenesis.
• Creatine kinase mitochondrial 1 (CKMT1), involved in energy metabolism, has an unknown role in intestinal inflammation.

Purpose of the Study:

• To investigate the role of CKMT1 in intestinal epithelial cells (IECs) during inflammation.
• To elucidate the mechanisms by which CKMT1 influences mitochondrial homeostasis and apoptosis in the context of inflammatory bowel disease (IBD).

Main Methods:

• Analysis of CKMT1 expression in UC patient colon tissues and dextran sodium sulfate (DSS)-induced colitis mouse models.
• Generation and study of intestinal epithelial-specific CKMT1 knockout mice.
• In vitro experiments using IECs to assess apoptosis pathways and reactive oxygen species (ROS) generation.

Main Results:

• CKMT1 expression was significantly decreased in colon tissues of UC patients and DSS-induced colitis mice.
• CKMT1 knockout in IECs impaired mitochondrial homeostasis, barrier function, and increased oxidative stress and apoptosis.
• CKMT1 deficiency enhanced TNF-α-induced mitochondrial ROS via reverse electron transfer (RET), leading to mPTP opening and apoptosis.

Conclusions:

• CKMT1 plays a crucial role in maintaining intestinal homeostasis and mitochondrial function.
• CKMT1 protects against intestinal inflammation by limiting ROS production and apoptosis.
• CKMT1 represents a potential therapeutic target for inflammatory bowel disease (IBD).