The yeast mitochondrial permeability transition is regulated by reactive oxygen species, endogenous Ca2+ and Cpr3, mediating cell death

Biochimica Et Biophysica Acta. Bioenergetics
Yoshiko KameiRei Asakai

Abstract

We investigated the properties of the permeability transition pore (PTP) in Saccharomyces cerevisiae in agar-embedded mitochondria (AEM) and agar-embedded cells (AEC) and its role in yeast death. In AEM, ethanol-induced pore opening, as indicated by the release of calcein and mitochondrial membrane depolarization, can be inhibited by CsA, by Cpr3 deficiency, and by the antioxidant glutathione. Notably, the pore opening is inhibited, when mitochondria are preloaded by EGTA or Fluo3 to chelate matrix Ca2+, or are pretreated with 4-Br A23187 to extract matrix Ca2+, prior to agar-embedding, or when pore opening is induced in the presence of EGTA; opened pores are re-closed by sequential treatment with CsA, 4-Br A23187 plus EGTA and NADH, indicating endogenous matrix Ca2+ involvement. CsA also inhibits the pore opening with low conductance triggered by exogenous Ca2+ transport with ETH129. In AEC, the treatment of tert-butylhydroperoxide, a pro-oxidant that triggers transient pore opening in high conductance in AEM, induces yeast death, which is also dependent on CsA and Cpr3. Furthermore, AEMs from mutants lacking three ADP/ATP carrier (AAC) isoforms and with defective ATP synthase dimerization exhibit high and low conductance pore...Continue Reading

Citations

Dec 14, 2018·Frontiers in Physiology·Valentina De ColMarco Zancani
Mar 2, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Vidhya BharathiBasant K Patel
Jun 14, 2020·Mitochondrion·Marco ZancaniGiovanna Lippe
Apr 26, 2021·Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology·Chrystian Rodriguez-ArmentaAdriana Muhlia-Almazan
Aug 18, 2020·Biochimica Et Biophysica Acta. Bioenergetics·Manuel Gutiérrez-Aguilar

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