The mitochondrial permeability transition from yeast to mammals

Abstract

a b s t r a c tRegulated permeability changes have been detected in mitochondria across species. We review here their key features, with the goal of assessing whether a ''permeability transition" similar to that observed in higher eukaryotes is present in other species. The recent discoveries (i) that treatment with cyclosporin A (CsA) unmasks an inhibitory site for inorganic phosphate (Pi) [Basso, E., Petronilli, V., Forte, M.A. and Bernardi, P. (2008) Phosphate is essential for inhibition of the mitochondrial permeability transition pore by cyclosporin A and by cyclophilin D ablation. J. Biol. Chem. 283, 26307-26311], the classical inhibitor of the permeability transition of yeast and (ii) that under proper experimental conditions a matrix Ca 2+ -dependence can be demonstrated in yeast as well

Cyclosporin A inhibits colon cancer cell growth independently of the calcineurin pathway

“…CsA has been shown to interfere with mitochondrial homeostasis, an effect not attributed to FK506. 37 Therefore, a mitochondria-mediated cell death could be at play. To test if the reduced viability was a consequence of necroptosis, we concomitantly treated CACO-2 cells with CsA and increasing concentrations of necrostatin 1 (Nec-1).…”

Hepatitis B virus X protein targets the Bcl-2 protein CED-9 to induce intracellular Ca 2+ increase and cell death in Caenorhabditis elegans

“…We first treated smIs98 animals with cyclosporin A (CsA), a peptide that desensitizes MPT by inhibiting the activity of the mitochondrial cyclophilin D, the essential regulatory component of MPT (35). In smIs98 animals that normally lost 50% of PLM neurons, CsA treatment reduced the percentage of missing PLMs to 15% (Fig.…”

Channel Formation by Yeast F-ATP Synthase and the Role of Dimerization in the Mitochondrial Permeability Transition

“…Inner membrane permeability pathways have been described in yeast (9) and in Drosophila melanogaster (10), but whether these coincide with the mammalian PTP remains an open question (11)(12)(13)(14). The issue is particularly complex in the case of yeast, where multiple conductance pathways may exist including an uncoupling protein-independent permeability activated by ATP (15)(16)(17).…”