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Functional activity and morphology of isolated rat cardiac mitochondria under calcium overload. Effect of naringin

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Abstract

The function of mitochondria as a regulator of myocyte calcium homeostasis has been extensively discussed. The aim of the present work was further clarification of the details of modulation of the functional activity of rat cardiac mitochondria by exogenous Ca2+ ions either in the absence or in the presence of the plant flavonoid naringin. Low free Ca2+ concentrations (40–250 nM) effectively inhibited the respiratory activity of heart mitochondria, remaining unaffected the efficacy of oxygen consumption. In the presence of high exogenous Ca2+ ion concentrations (Ca2+ free was 550 µM), we observed a dramatic increase in mitochondrial heterogeneity in size and electron density, which was related to calcium-induced opening of the mitochondrial permeability transition pores (MPTP) and membrane depolarization (Ca2+free ions were from 150 to 750 µM). Naringin partially prevented Ca2+-induced cardiac mitochondrial morphological transformations (200 µM) and dose-dependently inhibited the respiratory activity of mitochondria (10–75 µM) in the absence or in the presence of calcium ions. Our data suggest that naringin (75 µM) promoted membrane potential dissipation, diminishing the potential-dependent accumulation of calcium ions by mitochondria and inhibiting calcium-induced MPTP formation. The modulating effect of the flavonoid on Ca2+-induced mitochondria alterations may be attributed to the weak-acidic nature of the flavonoid and its protonophoric/ionophoric properties. Our results show that the sensitivity of rat heart mitochondria to Ca2+ ions was much lower in the case of MPTP opening and much higher in the case of respiration inhibition as compared to liver mitochondria.

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Abbreviations

ADP:

adenosine 5′-diphosphate sodium salt

ANT:

adenine nucleotide translocase

BKA:

bongkrekate

BSA:

bovine serum albumin

CsA:

cyclosporine A

EDTA :

ethylenediaminetetraacetic acid disodium salt

EGTA :

ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid tetrasodium salt

ER/SR:

endoplasmic/sarcoplasmic reticulum

FCCP:

carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone

HEPES:

4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid 

IFM:

interfibrillar mitochondria

Me:

median, MCU - mitochondrial Ca2+uniporter

MPTP:

mitochondrial permeability transition pores

PBS:

isotonic buffered saline

RCR:

respiratory control ratio

ROS:

reactive oxygen species

RuR:

Ruthenium red

SERCA:

sarcoplasmic reticulum Ca2+-ATPase

SSM:

subsarcolemmal mitochondria

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Acknowledgements

This study was partially supported by grant No М23KI – 14 for Joint scientific projects from the Belarusian Republican Foundation for Fundamental Research – National Scientific Foundation of China.

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Authors and Affiliations

  1. Department of Biochemistry, Yanka Kupala State University of Grodno, Bulvar Leninskogo Komsomola, 5, 230009, Grodno, Belarus

    T. A. Kavalenia, E. A. Lapshina, T. V. Ilyich & I. B. Zavodnik

  2. Institute of Biomechanics and Medical Engineering, Tsinghua University, Beijing, 100084, People’s Republic of China

    Hu-Cheng Zhao

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  1. T. A. Kavalenia
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  2. E. A. Lapshina
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  3. T. V. Ilyich
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  4. Hu-Cheng Zhao
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  5. I. B. Zavodnik
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Contributions

T.A. Kavalenia: investigation, data curation, software, E.A. Lapshina: data curation, validation, software, writing-original draft preparation, T.V. Ilyich: investigation, software, visualization, Hu-Cheng Zhao: conceptualization, methodology, supervision, I.B. Zavodnik: conceptualization, writing-reviewing and editing.All the authors approved the final version of the manuscript.

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Correspondence to I. B. Zavodnik.

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Kavalenia, T.A., Lapshina, E.A., Ilyich, T.V. et al. Functional activity and morphology of isolated rat cardiac mitochondria under calcium overload. Effect of naringin. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-024-04935-z

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