Identifying Compounds that Induce Opening of the Mitochondrial Permeability Transition Pore in Isolated Rat Liver Mitochondria. Issue 1 (27th May 2014)

• Record Type: Journal Article
• Authors: Marroquin, Lisa; Swiss, Rachel; Will, Yvonne
• Editors: Costa, Lucio G; Davila, Julio C.; Lawrence, David A.; Reed, Donald J.
• Is Part Of: Current protocols in toxicology. Volume 60:Issue 1(2014)
• Page Start: 25.4.1
• Page End: 25.4.17
• Publication Date: 2014-05-27
• Subjects: mitochondria permeability transition pore -- mitochondrial toxicity -- mitochondrial swelling; Toxicology -- Laboratory manuals; Toxicology -- methods; Toxicology; Laboratory Manual; Electronic books; Laboratory manuals; 571.95028
• DOI: 10.1002/0471140856.tx2504s60
• Languages: English
• ISSNs: 1934-9254

Abstract

Abstract: The mitochondrial permeability transition pore (MPTP) is a protein pore that forms in the inner mitochondrial membrane and allows the membrane to be permeable to all molecules of less than 1500 Da. Ca 2+, numerous reactive chemicals, and oxidative stress induce MPTP opening, whereas cyclosporin A (CsA) or bongkrekic acid block it. In addition, several drugs have been shown to induce MPTP opening, leading to the loss of mitochondrial membrane potential, swelling of the matrix because of water accumulation, rupture of the outer mitochondrial membrane, and release of intermembrane space proteins into the cytosol. This ultimately leads to the rupture of the outer mitochondrial membrane and cell demise. Here, we describe an assay using isolated rat liver mitochondria that can detect Ca 2+ ‐dependent drug‐induced opening of the MPTP, providing protocols for screening in both cuvette and 96‐well format. Curr. Protoc. Toxicol . 60:25.4.1:‐25.4.17. © 2014 by John Wiley & Sons, Inc.