Physiological levels of cardiolipin acutely affect mitochondrial respiration in vascular smooth muscle cells

Cardiolipin (CL) is a phospholipid molecule found in the inner mitochondrial membrane, where it normally associates with and activates the respiratory complexes. Following myocardial infarction, CL gets released from necrotic cells, consequently affecting neighboring tissues. We have previously demo...

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Main Authors: Deema Galambo, Andreas Bergdahl
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:Current Research in Physiology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2665944122000505
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author Deema Galambo
Andreas Bergdahl
author_facet Deema Galambo
Andreas Bergdahl
author_sort Deema Galambo
collection DOAJ
description Cardiolipin (CL) is a phospholipid molecule found in the inner mitochondrial membrane, where it normally associates with and activates the respiratory complexes. Following myocardial infarction, CL gets released from necrotic cells, consequently affecting neighboring tissues. We have previously demonstrated that physiological concentrations of up to 100 μM CL diminish endothelial cell migration and angiogenic sprouting. Since CL is vital to cellular life, we hypothesized that this molecule may have considerable implications on vascular smooth muscle cells bioenergetics, a key phase in atherogenesis. We examined the acute effects of physiological concentrations of CL on oxidative phosphorylation in permeabilized mice aorta using high-resolution respirometry and a substrate-inhibitor titration protocol. We found that CL significantly lowers LEAK and maximal State 3 respiration. In addition, we found that the acceptor control ratio, representing the coupling between oxidation and phosphorylation, was significantly upregulated by CL. Our findings demonstrate that in situ mitochondrial respiration in permeabilized smooth muscle cells is attenuated when physiological concentrations of CL are applied acutely. This could provide a novel therapy to reduce their dedifferentiation and consequently atherogenesis.
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spelling doaj.art-0248b03bac684d66ad45af33e69a75ba2023-12-09T06:07:50ZengElsevierCurrent Research in Physiology2665-94412023-01-016100097Physiological levels of cardiolipin acutely affect mitochondrial respiration in vascular smooth muscle cellsDeema Galambo0Andreas Bergdahl1Department of Biology, Concordia, Montreal, QC, CanadaDepartment of Health, Kinesiology & Applied Physiology, Concordia University, Montreal, QC, Canada; Corresponding author.Cardiolipin (CL) is a phospholipid molecule found in the inner mitochondrial membrane, where it normally associates with and activates the respiratory complexes. Following myocardial infarction, CL gets released from necrotic cells, consequently affecting neighboring tissues. We have previously demonstrated that physiological concentrations of up to 100 μM CL diminish endothelial cell migration and angiogenic sprouting. Since CL is vital to cellular life, we hypothesized that this molecule may have considerable implications on vascular smooth muscle cells bioenergetics, a key phase in atherogenesis. We examined the acute effects of physiological concentrations of CL on oxidative phosphorylation in permeabilized mice aorta using high-resolution respirometry and a substrate-inhibitor titration protocol. We found that CL significantly lowers LEAK and maximal State 3 respiration. In addition, we found that the acceptor control ratio, representing the coupling between oxidation and phosphorylation, was significantly upregulated by CL. Our findings demonstrate that in situ mitochondrial respiration in permeabilized smooth muscle cells is attenuated when physiological concentrations of CL are applied acutely. This could provide a novel therapy to reduce their dedifferentiation and consequently atherogenesis.http://www.sciencedirect.com/science/article/pii/S2665944122000505Vascular biologyVascular smooth muscle cellsBiological therapiesMitochondriaOxidative phosphorylation
spellingShingle Deema Galambo
Andreas Bergdahl
Physiological levels of cardiolipin acutely affect mitochondrial respiration in vascular smooth muscle cells
Current Research in Physiology
Vascular biology
Vascular smooth muscle cells
Biological therapies
Mitochondria
Oxidative phosphorylation
title Physiological levels of cardiolipin acutely affect mitochondrial respiration in vascular smooth muscle cells
title_full Physiological levels of cardiolipin acutely affect mitochondrial respiration in vascular smooth muscle cells
title_fullStr Physiological levels of cardiolipin acutely affect mitochondrial respiration in vascular smooth muscle cells
title_full_unstemmed Physiological levels of cardiolipin acutely affect mitochondrial respiration in vascular smooth muscle cells
title_short Physiological levels of cardiolipin acutely affect mitochondrial respiration in vascular smooth muscle cells
title_sort physiological levels of cardiolipin acutely affect mitochondrial respiration in vascular smooth muscle cells
topic Vascular biology
Vascular smooth muscle cells
Biological therapies
Mitochondria
Oxidative phosphorylation
url http://www.sciencedirect.com/science/article/pii/S2665944122000505
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