Mitochondrial dysfunction in inflammatory bowel disease.

Elizabeth A Novak,Kevin P Mollen

doi:10.3389/fcell.2015.00062

Abstract

Inflammatory Bowel Disease (IBD) represents a group of idiopathic disorders characterized by chronic or recurring inflammation of the gastrointestinal tract. While the exact etiology of disease is unknown, IBD is recognized to be a complex, multifactorial disease that results from an intricate interplay of genetic predisposition, an altered immune response, changes in the intestinal microbiota, and environmental factors. Together, these contribute to a destruction of the intestinal epithelial barrier, increased gut permeability, and an influx of immune cells. Given that most cellular functions as well as maintenance of the epithelial barrier is energy-dependent, it is logical to assume that mitochondrial dysfunction may play a key role in both the onset and recurrence of disease. Indeed several studies have demonstrated evidence of mitochondrial stress and alterations in mitochondrial function within the intestinal epithelium of patients with IBD and mice undergoing experimental colitis. Although the hallmarks of mitochondrial dysfunction, including oxidative stress and impaired ATP production are known to be evident in the intestines of patients with IBD, it is as yet unclear whether these processes occur as a cause of consequence of disease. We provide a current review of mitochondrial function in the setting of intestinal inflammation during IBD.

Highlights

Inflammatory Bowel DiseaseInflammatory bowel disease (IBD) is a complex, chronic, relapsing, and remitting inflammatory condition of the gastrointestinal tract characterized by symptoms such as diarrhea, bloody stools, abdominal pain, and weight loss (Greco et al, 2011; Indriolo et al, 2011; Rigoli and Caruso, 2014)
This study suggests that the UPRmt has a role in the pathogenesis of Inflammatory Bowel DiseaseInflammatory bowel disease (IBD), and since it seems that PKR integrates UPRmt signaling into unfolded protein response (UPRER), both mitochondrial and endoplasmic reticulum (ER) protein homeostatic responses might contribute to intestinal inflammation
There is no evidence for a causative association between mitochondrial dysfunction and IBD, here we provide several studies that demonstrate potential links connecting the two

Summary

Introduction

Inflammatory bowel disease (IBD) is a complex, chronic, relapsing, and remitting inflammatory condition of the gastrointestinal tract characterized by symptoms such as diarrhea, bloody stools, abdominal pain, and weight loss (Greco et al, 2011; Indriolo et al, 2011; Rigoli and Caruso, 2014). The integrity of the intestinal epithelium, tight junction maintenance, and β-oxidation are key cellular processes within the intestinal epithelium that are dependent upon properly functioning mitochondria, but are known to be altered in animal models of intestinal inflammation and in humans with IBD. It is possible that mitochondrial dysfunction could impact IEC differentiation either through energy production or signaling networks, adversely affecting the integrity of the epithelial cell barrier and potentially influencing the development of disease. Studies do suggest that both mitochondrial dysfunction (Lewis and McKay, 2009) and increased gut permeability (De-Souza and Greene, 2005; Deitch et al, 2006) affect the overall competence of the intestinal epithelial barrier, but the stimuli that initiates either process is not known. The interrelation of mitochondrial dysfunction, autophagy, and IBD is still elusive

Conclusion

Findings

Methods