Mitochondria Isolated from Hearts Subjected to Ischemia/Reperfusion Benefit from Adenine Nucleotide Translocase 1 Overexpression

Reperfusion is the only feasible therapy following myocardial infarction, but reperfusion has been shown to damage mitochondrial function and disrupt energy production in the heart. Adenine nucleotide translocase 1 (ANT1) facilitates the transfer of ADP/ATP across the inner mitochondrial membrane; t...

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Autores principales:	Andrea Dörner, Oleg Lynetskiy, Gerhild Euler, Ulf Landmesser, Klaus-Dieter Schlüter, Jacqueline Heger
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	adenine nucleotide translocase 1 (ANT1) Langendorff-perfused hearts mitochondria ischemia/reperfusion (I/R) Chemical technology TP1-1185 Chemical engineering TP155-156
Acceso en línea:	https://doaj.org/article/d4f416391d3e4ca0854d6ee3bdf84e29
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spelling	oai:doaj.org-article:d4f416391d3e4ca0854d6ee3bdf84e292021-11-25T18:19:42ZMitochondria Isolated from Hearts Subjected to Ischemia/Reperfusion Benefit from Adenine Nucleotide Translocase 1 Overexpression10.3390/membranes111108362077-0375https://doaj.org/article/d4f416391d3e4ca0854d6ee3bdf84e292021-10-01T00:00:00Zhttps://www.mdpi.com/2077-0375/11/11/836https://doaj.org/toc/2077-0375Reperfusion is the only feasible therapy following myocardial infarction, but reperfusion has been shown to damage mitochondrial function and disrupt energy production in the heart. Adenine nucleotide translocase 1 (ANT1) facilitates the transfer of ADP/ATP across the inner mitochondrial membrane; therefore, we tested whether ANT1 exerts protective effects on mitochondrial function during ischemia/reperfusion (I/R). The hearts of wild-type (WT) and transgenic ANT1-overexpressing (ANT1-TG) rats were exposed to I/R injury using the standard Langendorff technique, after which mitochondrial function, hemodynamic parameters, infarct size, and components of the contractile apparatus were determined. ANT1-TG hearts expressed higher ANT protein levels, with reduced levels of oxidative 4-hydroxynonenal ANT modifications following I/R. ANT1-TG mitochondria isolated from I/R hearts displayed stable calcium retention capacity (CRC) and improved membrane potential stability compared with WT mitochondria. Mitochondria isolated from ANT1-TG hearts experienced less restricted oxygen consumption than WT mitochondria after I/R. Left ventricular diastolic pressure (Pdia) decreased in ANT1-TG hearts compared with WT hearts following I/R. Preserved diastolic function was accompanied by a decrease in the phospho-lamban (PLB)/sarcoplasmic reticulum calcium ATPase (SERCA2a) ratio in ANT1-TG hearts compared with that in WT hearts. In addition, the phosphorylated (P)-PLB/PLB ratio increased in ANT1-TG hearts after I/R but not in WT hearts, which indicated more effective calcium uptake into the sarcoplasmic reticulum in ANT1-TG hearts. In conclusion, ANT1-TG rat hearts coped more efficiently with I/R than WT rat hearts, which was reflected by preserved mitochondrial energy balance, diastolic function, and calcium dynamics after reperfusion.Andrea DörnerOleg LynetskiyGerhild EulerUlf LandmesserKlaus-Dieter SchlüterJacqueline HegerMDPI AGarticleadenine nucleotide translocase 1 (ANT1)Langendorff-perfused heartsmitochondriaischemia/reperfusion (I/R)Chemical technologyTP1-1185Chemical engineeringTP155-156ENMembranes, Vol 11, Iss 836, p 836 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adenine nucleotide translocase 1 (ANT1) Langendorff-perfused hearts mitochondria ischemia/reperfusion (I/R) Chemical technology TP1-1185 Chemical engineering TP155-156
spellingShingle	adenine nucleotide translocase 1 (ANT1) Langendorff-perfused hearts mitochondria ischemia/reperfusion (I/R) Chemical technology TP1-1185 Chemical engineering TP155-156 Andrea Dörner Oleg Lynetskiy Gerhild Euler Ulf Landmesser Klaus-Dieter Schlüter Jacqueline Heger Mitochondria Isolated from Hearts Subjected to Ischemia/Reperfusion Benefit from Adenine Nucleotide Translocase 1 Overexpression
description	Reperfusion is the only feasible therapy following myocardial infarction, but reperfusion has been shown to damage mitochondrial function and disrupt energy production in the heart. Adenine nucleotide translocase 1 (ANT1) facilitates the transfer of ADP/ATP across the inner mitochondrial membrane; therefore, we tested whether ANT1 exerts protective effects on mitochondrial function during ischemia/reperfusion (I/R). The hearts of wild-type (WT) and transgenic ANT1-overexpressing (ANT1-TG) rats were exposed to I/R injury using the standard Langendorff technique, after which mitochondrial function, hemodynamic parameters, infarct size, and components of the contractile apparatus were determined. ANT1-TG hearts expressed higher ANT protein levels, with reduced levels of oxidative 4-hydroxynonenal ANT modifications following I/R. ANT1-TG mitochondria isolated from I/R hearts displayed stable calcium retention capacity (CRC) and improved membrane potential stability compared with WT mitochondria. Mitochondria isolated from ANT1-TG hearts experienced less restricted oxygen consumption than WT mitochondria after I/R. Left ventricular diastolic pressure (Pdia) decreased in ANT1-TG hearts compared with WT hearts following I/R. Preserved diastolic function was accompanied by a decrease in the phospho-lamban (PLB)/sarcoplasmic reticulum calcium ATPase (SERCA2a) ratio in ANT1-TG hearts compared with that in WT hearts. In addition, the phosphorylated (P)-PLB/PLB ratio increased in ANT1-TG hearts after I/R but not in WT hearts, which indicated more effective calcium uptake into the sarcoplasmic reticulum in ANT1-TG hearts. In conclusion, ANT1-TG rat hearts coped more efficiently with I/R than WT rat hearts, which was reflected by preserved mitochondrial energy balance, diastolic function, and calcium dynamics after reperfusion.
format	article
author	Andrea Dörner Oleg Lynetskiy Gerhild Euler Ulf Landmesser Klaus-Dieter Schlüter Jacqueline Heger
author_facet	Andrea Dörner Oleg Lynetskiy Gerhild Euler Ulf Landmesser Klaus-Dieter Schlüter Jacqueline Heger
author_sort	Andrea Dörner
title	Mitochondria Isolated from Hearts Subjected to Ischemia/Reperfusion Benefit from Adenine Nucleotide Translocase 1 Overexpression
title_short	Mitochondria Isolated from Hearts Subjected to Ischemia/Reperfusion Benefit from Adenine Nucleotide Translocase 1 Overexpression
title_full	Mitochondria Isolated from Hearts Subjected to Ischemia/Reperfusion Benefit from Adenine Nucleotide Translocase 1 Overexpression
title_fullStr	Mitochondria Isolated from Hearts Subjected to Ischemia/Reperfusion Benefit from Adenine Nucleotide Translocase 1 Overexpression
title_full_unstemmed	Mitochondria Isolated from Hearts Subjected to Ischemia/Reperfusion Benefit from Adenine Nucleotide Translocase 1 Overexpression
title_sort	mitochondria isolated from hearts subjected to ischemia/reperfusion benefit from adenine nucleotide translocase 1 overexpression
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d4f416391d3e4ca0854d6ee3bdf84e29
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Mitochondria Isolated from Hearts Subjected to Ischemia/Reperfusion Benefit from Adenine Nucleotide Translocase 1 Overexpression

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