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Cardiac Function is not Susceptible to Moderate Disassembly of Mitochondrial Respiratory Supercomplexes

Mitochondrial respiratory chain supercomplexes (RCS), particularly, the respirasome, which contains complexes I, III, and IV, have been suggested to participate in facilitating electron transport, reducing the production of reactive oxygen species (ROS), and maintaining the structural integrity of i...

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Autores principales: Chapa-Dubocq, Xavier R., Rodríguez-Graciani, Keishla M., Guzmán-Hernández, Roberto A., Jang, Sehwan, Brookes, Paul S., Javadov, Sabzali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084778/
https://www.ncbi.nlm.nih.gov/pubmed/32106430
http://dx.doi.org/10.3390/ijms21051555
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author Chapa-Dubocq, Xavier R.
Rodríguez-Graciani, Keishla M.
Guzmán-Hernández, Roberto A.
Jang, Sehwan
Brookes, Paul S.
Javadov, Sabzali
author_facet Chapa-Dubocq, Xavier R.
Rodríguez-Graciani, Keishla M.
Guzmán-Hernández, Roberto A.
Jang, Sehwan
Brookes, Paul S.
Javadov, Sabzali
author_sort Chapa-Dubocq, Xavier R.
collection PubMed
description Mitochondrial respiratory chain supercomplexes (RCS), particularly, the respirasome, which contains complexes I, III, and IV, have been suggested to participate in facilitating electron transport, reducing the production of reactive oxygen species (ROS), and maintaining the structural integrity of individual electron transport chain (ETC) complexes. Disassembly of the RCS has been observed in Barth syndrome, neurodegenerative and cardiovascular diseases, diabetes mellitus, and aging. However, the physiological role of RCS in high energy-demanding tissues such as the heart remains unknown. This study elucidates the relationship between RCS assembly and cardiac function. Adult male Sprague Dawley rats underwent Langendorff retrograde perfusion in the presence and absence of ethanol, isopropanol, or rotenone (an ETC complex I inhibitor). We found that ethanol had no effects on cardiac function, whereas rotenone reduced heart contractility, which was not recovered when rotenone was excluded from the perfusion medium. Blue native polyacrylamide gel electrophoresis revealed significant reductions of respirasome levels in ethanol- or rotenone-treated groups compared to the control group. In addition, rotenone significantly increased while ethanol had no effect on mitochondrial ROS production. In isolated intact mitochondria in vitro, ethanol did not affect respirasome assembly; however, acetaldehyde, a byproduct of ethanol metabolism, induced dissociation of respirasome. Isopropanol, a secondary alcohol which was used as an alternative compound, had effects similar to ethanol on heart function, respirasome levels, and ROS production. In conclusion, ethanol and isopropanol reduced respirasome levels without any noticeable effect on cardiac parameters, and cardiac function is not susceptible to moderate reductions of RCS.
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spelling pubmed-70847782020-03-24 Cardiac Function is not Susceptible to Moderate Disassembly of Mitochondrial Respiratory Supercomplexes Chapa-Dubocq, Xavier R. Rodríguez-Graciani, Keishla M. Guzmán-Hernández, Roberto A. Jang, Sehwan Brookes, Paul S. Javadov, Sabzali Int J Mol Sci Article Mitochondrial respiratory chain supercomplexes (RCS), particularly, the respirasome, which contains complexes I, III, and IV, have been suggested to participate in facilitating electron transport, reducing the production of reactive oxygen species (ROS), and maintaining the structural integrity of individual electron transport chain (ETC) complexes. Disassembly of the RCS has been observed in Barth syndrome, neurodegenerative and cardiovascular diseases, diabetes mellitus, and aging. However, the physiological role of RCS in high energy-demanding tissues such as the heart remains unknown. This study elucidates the relationship between RCS assembly and cardiac function. Adult male Sprague Dawley rats underwent Langendorff retrograde perfusion in the presence and absence of ethanol, isopropanol, or rotenone (an ETC complex I inhibitor). We found that ethanol had no effects on cardiac function, whereas rotenone reduced heart contractility, which was not recovered when rotenone was excluded from the perfusion medium. Blue native polyacrylamide gel electrophoresis revealed significant reductions of respirasome levels in ethanol- or rotenone-treated groups compared to the control group. In addition, rotenone significantly increased while ethanol had no effect on mitochondrial ROS production. In isolated intact mitochondria in vitro, ethanol did not affect respirasome assembly; however, acetaldehyde, a byproduct of ethanol metabolism, induced dissociation of respirasome. Isopropanol, a secondary alcohol which was used as an alternative compound, had effects similar to ethanol on heart function, respirasome levels, and ROS production. In conclusion, ethanol and isopropanol reduced respirasome levels without any noticeable effect on cardiac parameters, and cardiac function is not susceptible to moderate reductions of RCS. MDPI 2020-02-25 /pmc/articles/PMC7084778/ /pubmed/32106430 http://dx.doi.org/10.3390/ijms21051555 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chapa-Dubocq, Xavier R.
Rodríguez-Graciani, Keishla M.
Guzmán-Hernández, Roberto A.
Jang, Sehwan
Brookes, Paul S.
Javadov, Sabzali
Cardiac Function is not Susceptible to Moderate Disassembly of Mitochondrial Respiratory Supercomplexes
title Cardiac Function is not Susceptible to Moderate Disassembly of Mitochondrial Respiratory Supercomplexes
title_full Cardiac Function is not Susceptible to Moderate Disassembly of Mitochondrial Respiratory Supercomplexes
title_fullStr Cardiac Function is not Susceptible to Moderate Disassembly of Mitochondrial Respiratory Supercomplexes
title_full_unstemmed Cardiac Function is not Susceptible to Moderate Disassembly of Mitochondrial Respiratory Supercomplexes
title_short Cardiac Function is not Susceptible to Moderate Disassembly of Mitochondrial Respiratory Supercomplexes
title_sort cardiac function is not susceptible to moderate disassembly of mitochondrial respiratory supercomplexes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084778/
https://www.ncbi.nlm.nih.gov/pubmed/32106430
http://dx.doi.org/10.3390/ijms21051555
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