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RAS BiologyБиологические мембраны Membrane and Cell Biology

  • ISSN (Print) 0233-4755
  • ISSN (Online) 3034-5219

MKT-077 Suppresses the Functional Activity of Isolated Mouse Skeletal Muscle Mitochondria

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PII
S30345219S0233475525030037-1
DOI
10.7868/S3034521925030037
Publication type
Article
Status
Published
Authors
A. D. Igoshkina
  • Affiliation: Mari State University
N. V. Mikina
  • Affiliation: Mari State University
A. V. Chulkov
  • Affiliation: Mari State University
E. I. Khoroshavina
  • Affiliation: Mari State University
M. V. Dubinin
  • Affiliation: Mari State University
Volume/ Edition
Volume 42 / Issue number 3
Pages
197-208
Abstract
This study demonstrates the effect of the rhodocyanine derivative MKT-077 on the function of isolated mitochondria from mouse skeletal muscle. MKT-077 was shown to dose-dependently inhibit mitochondrial respiration fueled by glutamate/malate (complex I substrates) or succinate (complex II substrate). This effect of MKT-077 was accompanied by a decrease in the membrane potential of organelles and was associated with both inhibition of the activity of complexes I and II of the mitochondrial respiratory chain and an increase in the proton permeability of the inner mitochondrial membrane. Molecular docking revealed sites in mitochondrial respiratory chain complex I that have an affinity for MKT-077 comparable to that of the specific inhibitor rotenone. At a concentration of 5 µM, MKT-077 caused a significant increase in hydrogen peroxide production by skeletal muscle mitochondria. However, 1 µM MKT-077 reduced the pro-oxidant effect of antimycin A. In addition, MKT-077 dose-dependently reduced the ability of mitochondria to uptake and retain calcium ions in the matrix. The article discusses the mechanisms of possible action of MKT-077 on the functioning of skeletal muscle mitochondria and their contribution to the side effects observed during the therapy of pathological conditions in vivo using this rhodocyanine derivative.
Keywords
митохондрии скелетных мышц MKT-077 окислительное фосфорилирование дыхательная цепь активные формы кислорода кальций
Date of publication
16.02.2025
Year of publication
2025
Number of purchasers
0
Views
29

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