ER Proteotoxic Stress Drives Mitochondrial Dysfunction in Heat-Stressed Intestinal Epithelial Cells.

Area of Science:

• Animal Science
• Cell Biology
• Environmental Science

Background:

• Climate change exacerbates heat waves, threatening livestock production.
• Heat stress disrupts intestinal barrier integrity, leading to cellular injury.
• Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are known cellular consequences of heat stress.

Purpose of the Study:

• To investigate the causal link between ER stress and mitochondrial dysfunction in heat-stressed enterocytes.
• To elucidate the molecular mechanisms underlying heat stress-induced intestinal injury in livestock.
• To explore therapeutic strategies targeting ER stress for mitigating heat stress effects.

Main Methods:

• Utilized integrated transcriptomic, metabolomic, and functional analyses in porcine intestinal epithelial cells (IPEC-J2).
• Assessed mitochondrial bioenergetics and cellular ultrastructure under acute heat stress.
• Employed pharmacological inhibition and induction of ER stress to validate findings.

Main Results:

• Heat stress induced significant transcriptional and metabolic reprogramming, including ER stress activation.
• Mitochondrial bioenergetics were severely impaired, with reduced respiration and ATP production.
• Pharmacological inhibition of ER stress attenuated mitochondrial dysfunction and cellular damage.

Conclusions:

• Heat stress-induced ER stress critically mediates mitochondrial dysfunction and intestinal injury in enterocytes.
• Targeting ER stress presents a promising therapeutic strategy to mitigate heat stress-induced intestinal damage in livestock.
• Understanding these cellular mechanisms is vital for maintaining livestock health and productivity under climate change.