Keeping mitochondria happy - benefits of a pore choice in acute pancreatitis



Criddle, David N ORCID: 0000-0003-2952-8450
(2019) Keeping mitochondria happy - benefits of a pore choice in acute pancreatitis. JOURNAL OF PHYSIOLOGY, 597 (24). 5741 - 5742.

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Abstract

Mitochondrial dysfunction is a key feature of multiple diseases and thus protection of this organelle is an important therapeutic objective. The pancreatic acinar cell, which synthesises and stores digestive enzyme precursors, is the most abundant cell type in pancreatic tissue and considered to be the primary site of acute pancreatitis (AP) initiation. Early investigations at the University of Liverpool and by others discovered that precipitants of AP, including bile acids and alcohol non‐oxidative metabolites, disrupt calcium signalling in acinar cells leading to toxicity. Sustained cytosolic calcium elevations raise mitochondrial matrix calcium, triggering the opening of the mitochondrial permeability transition pore (MPTP), which results in a loss of membrane potential and ATP production vital for cellular processes (Criddle et al . 2006; Mukherjee et al . 2016) (Fig. 1). The prime consequence of pancreatic mitochondrial dysfunction in AP is necrotic cell death, the extent of which is a major determinant of clinical outcome. Subsequent studies have shown that calcium‐dependent mitochondrial dysfunction in response to AP precipitants also occurs in ductal cells, widening the cast of players implicated in the development of AP (Hegyi & Petersen, 2013). There is currently no specific therapy for the disease and protection of mitochondria by MPTP inhibition is considered a promising therapeutic approach.

Item Type: Article
Uncontrolled Keywords: acute pancreatitis, cyclophilin D, mitochondrial transition pore
Depositing User: Symplectic Admin
Date Deposited: 07 Nov 2019 10:25
Last Modified: 25 Jan 2022 18:18
DOI: 10.1113/JP279116
Open Access URL: https://doi.org/10.1113/JP279116
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3060874