Mitochondria and Inflammatory Bowel Diseases: Toward a Stratified Therapeutic Intervention

Overview

Journal Annu Rev Physiol

Publisher Annual Reviews

Specialty Physiology

Date 2021 Oct 6

PMID 34614372

Citations 32

Authors

Gwo-Tzer Ho

Arianne L Theiss

Affiliations

Soon will be listed here.

Abstract

Mitochondria serve numerous critical cellular functions, rapidly responding to extracellular stimuli and cellular demands while dynamically communicating with other organelles. Mitochondrial function in the gastrointestinal epithelium plays a critical role in maintaining intestinal health. Emerging studies implicate the involvement of mitochondrial dysfunction in inflammatory bowel disease (IBD). This review presents mitochondrial metabolism, function, and quality control that converge in intestinal epithelial stemness, differentiation programs, barrier integrity, and innate immunity to influence intestinal inflammation. Intestinal and disease characteristics that set the stage for mitochondrial dysfunction being a key factor in IBD and, in turn, pathogenic mitochondrial mechanisms influencing and potentiating the development of IBD, are discussed. These findings establish the basis for potential mitochondrial-targeted interventions for IBD therapy.

Citing Articles

CKMT1 deficiency contributes to mitochondrial dysfunction and promotes intestinal epithelial cell apoptosis via reverse electron transfer-derived ROS in colitis.

Wang Z, Wu H, Chang X, Song Y, Chen Y, Yan Z Cell Death Dis. 2025; 16(1):177.

PMID: 40089459 DOI: 10.1038/s41419-025-07504-4.

Systematic Identification of Mitochondrial Signatures in Alzheimer's Disease and Inflammatory Bowel Disease.

Wang F, Wang J, Chen T, Wang S, Meng X, Shen Y Mol Neurobiol. 2025; .

PMID: 40085351 DOI: 10.1007/s12035-025-04826-4.

Engineered mitochondria in diseases: mechanisms, strategies, and applications.

Li M, Wu L, Si H, Wu Y, Liu Y, Zeng Y Signal Transduct Target Ther. 2025; 10(1):71.

PMID: 40025039 PMC: 11873319. DOI: 10.1038/s41392-024-02081-y.

Unlocking Gut Health: The Potent Role of Stilbenoids in Intestinal Homeostasis.

Meng T, Wen Z, Cheng X, Li C, Zhang P, Xiao D Animals (Basel). 2025; 15(3).

PMID: 39943187 PMC: 11816141. DOI: 10.3390/ani15030417.

A potential therapeutic approach for ulcerative colitis: targeted regulation of mitochondrial dynamics and mitophagy through phytochemicals.

Zhou J, Xi Y, Wu T, Zeng X, Yuan J, Peng L Front Immunol. 2025; 15():1506292.

PMID: 39840057 PMC: 11747708. DOI: 10.3389/fimmu.2024.1506292.

References

Rath E, Haller D . Mitochondria at the interface between danger signaling and metabolism: role of unfolded protein responses in chronic inflammation. Inflamm Bowel Dis. 2011; 18(7):1364-77. DOI: 10.1002/ibd.21944. View

Faas M, de Vos P . Mitochondrial function in immune cells in health and disease. Biochim Biophys Acta Mol Basis Dis. 2020; 1866(10):165845. DOI: 10.1016/j.bbadis.2020.165845. View

Jostins L, Ripke S, Weersma R, Duerr R, McGovern D, Hui K . Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012; 491(7422):119-24. PMC: 3491803. DOI: 10.1038/nature11582. View

Ni H, Williams J, Ding W . Mitochondrial dynamics and mitochondrial quality control. Redox Biol. 2014; 4:6-13. PMC: 4309858. DOI: 10.1016/j.redox.2014.11.006. View

Beyaz S, Mana M, Roper J, Kedrin D, Saadatpour A, Hong S . High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature. 2016; 531(7592):53-8. PMC: 4846772. DOI: 10.1038/nature17173. View

Pagliarini D, Calvo S, Chang B, Sheth S, Vafai S, Ong S . A mitochondrial protein compendium elucidates complex I disease biology. Cell. 2008; 134(1):112-23. PMC: 2778844. DOI: 10.1016/j.cell.2008.06.016. View

Rogala A, Schoenborn A, Fee B, Cantillana V, Joyce M, Gharaibeh R . Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice. Dis Model Mech. 2018; 11(2). PMC: 5894938. DOI: 10.1242/dmm.031070. View

Kuhlbrandt W . Structure and function of mitochondrial membrane protein complexes. BMC Biol. 2015; 13:89. PMC: 4625866. DOI: 10.1186/s12915-015-0201-x. View

Clevers H, Bevins C . Paneth cells: maestros of the small intestinal crypts. Annu Rev Physiol. 2013; 75:289-311. DOI: 10.1146/annurev-physiol-030212-183744. View

10.

Van Houten B, Woshner V, Santos J . Role of mitochondrial DNA in toxic responses to oxidative stress. DNA Repair (Amst). 2005; 5(2):145-52. DOI: 10.1016/j.dnarep.2005.03.002. View

11.

Lawrence M, Huber W, Pages H, Aboyoun P, Carlson M, Gentleman R . Software for computing and annotating genomic ranges. PLoS Comput Biol. 2013; 9(8):e1003118. PMC: 3738458. DOI: 10.1371/journal.pcbi.1003118. View

12.

Repici M, Giorgini F . DJ-1 in Parkinson's Disease: Clinical Insights and Therapeutic Perspectives. J Clin Med. 2019; 8(9). PMC: 6780414. DOI: 10.3390/jcm8091377. View

13.

OMorain C, Smethurst P, Levi J, Peters T . Subcellular fractionation of rectal biopsy homogenates from patients with inflammatory bowel disease. Scand J Gastroenterol. 1985; 20(2):209-14. DOI: 10.3109/00365528509089659. View

14.

Roy S, Esmaeilniakooshkghazi A, Patnaik S, Wang Y, George S, Ahrorov A . Villin-1 and Gelsolin Regulate Changes in Actin Dynamics That Affect Cell Survival Signaling Pathways and Intestinal Inflammation. Gastroenterology. 2017; 154(5):1405-1420.e2. PMC: 7808315. DOI: 10.1053/j.gastro.2017.12.016. View

15.

Ikumoto T, Hayashi S, Tomita S, Miwa S, Mitomi H, Fujimori T . Manganese superoxide dismutase plays an important role in the inflammatory process and predicts disease severity and activity in patients with ulcerative colitis. APMIS. 2014; 122(6):512-7. PMC: 4226327. DOI: 10.1111/apm.12192. View

16.

Barker N, van Oudenaarden A, Clevers H . Identifying the stem cell of the intestinal crypt: strategies and pitfalls. Cell Stem Cell. 2012; 11(4):452-60. DOI: 10.1016/j.stem.2012.09.009. View

17.

Chaanine A, Kohlbrenner E, Gamb S, Guenzel A, Klaus K, Fayyaz A . FOXO3a regulates BNIP3 and modulates mitochondrial calcium, dynamics, and function in cardiac stress. Am J Physiol Heart Circ Physiol. 2016; 311(6):H1540-H1559. PMC: 5206339. DOI: 10.1152/ajpheart.00549.2016. View

18.

Windsor J, Kaplan G . Evolving Epidemiology of IBD. Curr Gastroenterol Rep. 2019; 21(8):40. DOI: 10.1007/s11894-019-0705-6. View

19.

Mirkov M, Verstockt B, Cleynen I . Genetics of inflammatory bowel disease: beyond NOD2. Lancet Gastroenterol Hepatol. 2017; 2(3):224-234. DOI: 10.1016/S2468-1253(16)30111-X. View

20.

Bellot G, Garcia-Medina R, Gounon P, Chiche J, Roux D, Pouyssegur J . Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol. 2009; 29(10):2570-81. PMC: 2682037. DOI: 10.1128/MCB.00166-09. View