Molecular Mechanism and Potential Role of Mitophagy in Acute Pancreatitis

Overview

Journal Mol Med

Publisher Biomed Central

Specialties General Medicine
Molecular Biology

Date 2024 Sep 3

PMID 39227768

Authors

Lili Zhu

Yunfei Xu

Jian Lei

Affiliations

Soon will be listed here.

Abstract

Acute pancreatitis (AP) is a multifaceted inflammatory disorder stemming from the aberrant activation of trypsin within the pancreas. Despite the contribution of various factors to the pathogenesis of AP, such as trypsin activation, dysregulated increases in cytosolic Ca levels, inflammatory cascade activation, and mitochondrial dysfunction, the precise molecular mechanisms underlying the disease are still not fully understood. Mitophagy, a cellular process that preserves mitochondrial homeostasis under stress, has emerged as a pivotal player in the context of AP. Research suggests that augmenting mitophagy can mitigate pancreatic injury by clearing away malfunctioning mitochondria. Elucidating the role of mitophagy in AP may pave the way for novel therapeutic strategies. This review article aims to synthesize the current research findings on mitophagy in AP and underscore its significance in the clinical management of the disorder.

References

Jung K, Song S, Yi T, Jeon M, Hong S, Zheng H . Human bone marrow-derived clonal mesenchymal stem cells inhibit inflammation and reduce acute pancreatitis in rats. Gastroenterology. 2010; 140(3):998-1008. DOI: 10.1053/j.gastro.2010.11.047. View

Green D, Levine B . To be or not to be? How selective autophagy and cell death govern cell fate. Cell. 2014; 157(1):65-75. PMC: 4020175. DOI: 10.1016/j.cell.2014.02.049. View

Ojeda D, Grasso D, Urquiza J, Till A, Vaccaro M, Quarleri J . Cell Death Is Counteracted by Mitophagy in HIV-Productively Infected Astrocytes but Is Promoted by Inflammasome Activation Among Non-productively Infected Cells. Front Immunol. 2018; 9:2633. PMC: 6255949. DOI: 10.3389/fimmu.2018.02633. View

Pandol S, Saluja A, Imrie C, Banks P . Acute pancreatitis: bench to the bedside. Gastroenterology. 2007; 132(3):1127-51. DOI: 10.1053/j.gastro.2007.01.055. View

Gukovsky I, Gukovskaya A . Impaired autophagy triggers chronic pancreatitis: lessons from pancreas-specific atg5 knockout mice. Gastroenterology. 2015; 148(3):501-5. PMC: 4443443. DOI: 10.1053/j.gastro.2015.01.012. View

Debnath J, Gammoh N, Ryan K . Autophagy and autophagy-related pathways in cancer. Nat Rev Mol Cell Biol. 2023; 24(8):560-575. PMC: 9980873. DOI: 10.1038/s41580-023-00585-z. View

Talukdar R, Sareen A, Zhu H, Yuan Z, Dixit A, Cheema H . Release of Cathepsin B in Cytosol Causes Cell Death in Acute Pancreatitis. Gastroenterology. 2016; 151(4):747-758.e5. PMC: 5037034. DOI: 10.1053/j.gastro.2016.06.042. View

Mao X, Zou W, Cao Y, Wang Y, Deng S, Cooper D . The CEL-HYB1 Hybrid Allele Promotes Digestive Enzyme Misfolding and Pancreatitis in Mice. Cell Mol Gastroenterol Hepatol. 2022; 14(1):55-74. PMC: 9117557. DOI: 10.1016/j.jcmgh.2022.03.013. View

Yu C, Merza M, Luo L, Thorlacius H . Inhibition of Ras signalling reduces neutrophil infiltration and tissue damage in severe acute pancreatitis. Eur J Pharmacol. 2014; 746:245-51. DOI: 10.1016/j.ejphar.2014.11.020. View

10.

Scaini G, Mason B, Diaz A, Jha M, Soares J, Trivedi M . Dysregulation of mitochondrial dynamics, mitophagy and apoptosis in major depressive disorder: Does inflammation play a role?. Mol Psychiatry. 2021; 27(2):1095-1102. DOI: 10.1038/s41380-021-01312-w. View

11.

Habtezion A, Gukovskaya A, Pandol S . Acute Pancreatitis: A Multifaceted Set of Organelle and Cellular Interactions. Gastroenterology. 2019; 156(7):1941-1950. PMC: 6613790. DOI: 10.1053/j.gastro.2018.11.082. View

12.

Ye W, Wen C, Zeng A, Hu X . Increased levels of circulating oxidized mitochondrial DNA contribute to chronic inflammation in metabolic syndrome, and MitoQ-based antioxidant therapy alleviates this DNA-induced inflammation. Mol Cell Endocrinol. 2022; 560:111812. DOI: 10.1016/j.mce.2022.111812. View

13.

Gardner T . Acute Pancreatitis. Ann Intern Med. 2021; 174(2):ITC17-ITC32. DOI: 10.7326/AITC202102160. View

14.

Tabassum S, Misrani A, Huang H, Zhang Z, Li Q, Long C . Resveratrol Attenuates Chronic Unpredictable Mild Stress-Induced Alterations in the SIRT1/PGC1α/SIRT3 Pathway and Associated Mitochondrial Dysfunction in Mice. Mol Neurobiol. 2023; 60(9):5102-5116. DOI: 10.1007/s12035-023-03395-8. View

15.

Banks P, Bollen T, Dervenis C, Gooszen H, Johnson C, Sarr M . Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2012; 62(1):102-11. DOI: 10.1136/gutjnl-2012-302779. View

16.

Mareninova O, Hermann K, French S, OKonski M, Pandol S, Webster P . Impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis. J Clin Invest. 2009; 119(11):3340-55. PMC: 2769194. DOI: 10.1172/JCI38674. View

17.

Biczo G, Vegh E, Shalbueva N, Mareninova O, Elperin J, Lotshaw E . Mitochondrial Dysfunction, Through Impaired Autophagy, Leads to Endoplasmic Reticulum Stress, Deregulated Lipid Metabolism, and Pancreatitis in Animal Models. Gastroenterology. 2017; 154(3):689-703. PMC: 6369139. DOI: 10.1053/j.gastro.2017.10.012. View

18.

Zhu J, Zhang S, Geng Y, Song Y . Transient receptor potential ankyrin 1 protects against sepsis-induced kidney injury by modulating mitochondrial biogenesis and mitophagy. Am J Transl Res. 2019; 10(12):4163-4172. PMC: 6325509. View

19.

Youle R, Narendra D . Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 2010; 12(1):9-14. PMC: 4780047. DOI: 10.1038/nrm3028. View

20.

Hashimoto D, Ohmuraya M, Hirota M, Yamamoto A, Suyama K, Ida S . Involvement of autophagy in trypsinogen activation within the pancreatic acinar cells. J Cell Biol. 2008; 181(7):1065-72. PMC: 2442206. DOI: 10.1083/jcb.200712156. View