Thapsigargin directly induces the mitochondrial permeability transition.

TitleThapsigargin directly induces the mitochondrial permeability transition.
Publication TypeJournal Article
Year of Publication1999
AuthorsKorge, P, Weiss, JN
JournalEur J Biochem
Volume265
Issue1
Pagination273-80
Date Published1999 Oct 01
ISSN0014-2956
KeywordsAnimals, Biological Transport, Calcium, Cyclosporins, Ion Channels, Mitochondria, Heart, Mitochondria, Liver, Mitochondrial Membrane Transport Proteins, Permeability, Rabbits, Thapsigargin
Abstract

High concentrations of thapsigargin (TG) have been used to study the process of necrotic cell death, which involves mitochondria in the cell rapidly undergoing the mitochondrial permeability transition (MPT). We therefore investigated the effects of TG on MPT in isolated liver and heart mitochondria. Using a matrix swelling assay in combination with a novel enzymatic method based on inner membrane permeability to citrate synthase substrates, TG induced MPT in a concentration-dependent manner, independent of extramitochondrial [Ca2+] and inhibitable by cyclosporin A. Evidence from alamethicin-permeabilized mitochondria suggests that TG induces MPT by causing Ca2+ release from mitochondrial matrix Ca2+-binding sites. These findings suggest that the MPT-inducing effect of TG may contribute to its pro-necrotic and pro-apoptotic effects in various cell types.

DOI10.1046/j.1432-1327.1999.00724.x
Alternate JournalEur. J. Biochem.
Citation Key10.1046/j.1432-1327.1999.00724.x
PubMed ID10491183
Grant ListP50 HL52319 / HL / NHLBI NIH HHS / United States