The Regulation of Non-Specific Membrane Permeability Transition in Yeast Mitochondria under Oxidative Stress

Elena P Isakova,Olga I Klein,Yulia I Deryabina

doi:10.3390/microbiolres12020029

Elena P Isakova, Olga I Klein + Show 1 more

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https://doi.org/10.3390/microbiolres12020029

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Abstract

In this study, the mechanism of non-specific membrane permeability (yPTP) in the Endomyces magnusii yeast mitochondria under oxidative stress due to blocking the key antioxidant enzymes has been investigated. We used monitoring the membrane potential at the cellular (potential-dependent staining) and mitochondrial levels and mitochondria ultra-structural images with transmission electron microscopy (TEM) to demonstrate the mitochondrial permeability transition induction due to the pore opening. Analysis of the yPTP opening upon respiring different substrates showed that NAD(P)H completely blocked the development of the yPTP. The yPTP opening was inhibited by 5–20 mM Pi, 5 mM Mg2+, adenine nucleotides (AN), 5 mM GSH, the inhibitor of the Pi transporter (PiC), 100 μM mersalyl, the blockers of the adenine nucleotide transporter (ANT) carboxyatractyloside (CATR), and bongkrekic acid (BA). We concluded that the non-specific membrane permeability pore opens in the E. magnusii mitochondria under oxidative stress, and the ANT and PiC are involved in its formation. The crucial role of the Ca2+ ions in the process has not been confirmed. We showed that the Ca2+ ions affected the yPTP both with and without the Ca2+ ionophore ETH129 application insignificantly. This phenomenon in the E. magnusii yeast unites both mitochondrial unselective channel (ScMUC) features in the Saccharomyces cerevisiae mitochondria and the classical membrane pore in the mammalian ones (mPTP).

Highlights

Non-specific membrane transition in animal mitochondria is a sudden increase in permeability of the inner mitochondria membrane for the compounds of Mr ≤ 1500 Da [1,2].The main features of the phenomenon have been investigated for about 40 years, since its discovery in heart mitochondria by Haworth and Hunter in 1979 [3,4,5]
It is considered that if the Ca2+ ions are bound under pathological conditions, namely oxidative stress, de-energization, depletion of the intra-mitochondria adenine nucleotides (AN), Ca2+ overload during ischemia/reperfusion, and some others, the complex can open a cyclosporin A (CsA)-sensitive membrane pore with a diameter of 2.6–2.9 nm
All the isolated yeast mitochondria demonstrated a high level of intactness, as seen from high respiratory rates in respiration state 3 and relatively high respiratory respiratory control (RC) (Table 1)

Summary

Introduction

Non-specific membrane transition in animal mitochondria (mPTP) is a sudden increase in permeability of the inner mitochondria membrane for the compounds of Mr ≤ 1500 Da [1,2].The main features of the phenomenon have been investigated for about 40 years, since its discovery in heart mitochondria by Haworth and Hunter in 1979 [3,4,5]. It is considered that if the Ca2+ ions are bound under pathological conditions, namely oxidative stress, de-energization, depletion of the intra-mitochondria adenine nucleotides (AN), Ca2+ overload during ischemia/reperfusion, and some others, the complex can open a cyclosporin A (CsA)-sensitive membrane pore with a diameter of 2.6–2.9 nm. It can pass the compounds with a low molecular weight, followed by the release of the accumulated. Carboxyatractyloside (CATR) [14,15], 3-hydroxybutyrate/polyphosphate [16], and fatty acids [17], along with the Ca2+ and Pi

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