NDLI: The inhibitors of antioxidant cell enzymes induce permeability transition in yeast mitochondria

Content Provider	Springer Nature Link
Author	Deryabina, Yulia Isakova, Elena Antipov, Alexey Saris, Nils Erik L.
Copyright Year	2013
Abstract	In this study we investigated the effects of exogenous and endogenous oxidative stress on mitochondrial membrane permeability transition in yeast cells. E. magnusii yeast was used in the study as it is the only yeast strain possessing a natural high-capacity Са$^{2+}$ transport system. The key reactive oxygen species (ROS) detoxifying enzymes in the yeast cells - catalases (CATs) and superoxide dismutases (SODs) - were fully characterized. At least five isoforms of SODs and only one isoform of CATs were found in the E. magnusii mitochondria. The assessment of the main properties of mitochondrial non-specific permeability under physiological conditions such as dynamics of the membrane potential (∆Ψ) and swelling in mitochondria showed that under physiological conditions classical inhibitors of CATs (ATZ - 3-amino-1, 2, 4-triazole) and of SODs (DDC - diethyldithiocarbamate) caused irreversible decline in ∆Ψ in the yeast mitochondria. This decline was accelerated in the presence of 500 μM Са$^{2+}$. The combined action of the inhibitors (ATZ + DDC) promoted moderate swelling in the isotonic medium, which was confirmed by transmission electron microscopy. Mitochondrial swelling in the cells exposed to antioxidant system inhibitors was accompanied by typical signs of early apoptosis, namely by chromatin margination and condensation, vacuolization of the cytosol, and damage of the plasma membrane. Here we showed, at both cellular and mitochondrial levels, that the deregulation of oxidant-scavenging enzymes directly leads to the opening of the mPTP, followed by induction of apoptotic markers in the whole yeast cells. Our studies are the first to clarify the highly contradictory data in the literature on mPTP in yeast mitochondria.
Starting Page	491
Ending Page	504
Page Count	14
File Format	PDF
ISSN	0145479X
Journal	Journal of Bioenergetics and Biomembranes
Volume Number	45
Issue Number	5
e-ISSN	15736881
Language	English
Publisher	Springer US
Publisher Date	2013-04-27
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Ca$^{2+}$ Mitochondria Yeast Permeability transition pore Antioxidant enzymes Apoptosis Bioorganic Chemistry Biochemistry Animal Anatomy / Morphology / Histology Animal Biochemistry Organic Chemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Physiology

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