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Mitochondrial Oxidative Phosphorylation defect in the Heart of Subjects with Coronary Artery Disease. Sci Rep 2019 05 20;9(1):7623

Date

05/22/2019

Pubmed ID

31110224

Pubmed Central ID

PMC6527853

DOI

10.1038/s41598-019-43761-y

Scopus ID

2-s2.0-85066048228   12 Citations

Abstract

Coronary artery disease (CAD) is a leading cause of death worldwide and frequently associated with mitochondrial dysfunction. Detailed understanding of abnormalities in mitochondrial function that occur in patients with CAD is lacking. We evaluated mitochondrial damage, energy production, and mitochondrial complex activity in human non-CAD and CAD hearts. Fresh and frozen human heart tissue was used. Cell lysate or mitochondria were isolated using standard techniques. Mitochondrial DNA (mtDNA), NAD + and ATP levels, and mitochondrial oxidative phosphorylation capacity were evaluated. Proteins critical to the regulation of mitochondrial metabolism and function were also evaluated in tissue lysates. PCR analysis revealed an increase in mtDNA lesions and the frequency of mitochondrial common deletion, both established markers for impaired mitochondrial integrity in CAD compared to non-CAD patient samples. NAD+ and ATP levels were significantly decreased in CAD subjects compared to Non-CAD (NAD+ fold change: non-CAD 1.00 ± 0.17 vs. CAD 0.32 ± 0.12* and ATP fold change: non-CAD 1.00 ± 0.294 vs. CAD 0.01 ± 0.001*; N = 15, P < 0.005). We observed decreased respiration control index in CAD tissue and decreased activity of complexes I, II, and III. Expression of ETC complex subunits and respirasome formation were increased; however, elevations in the de-active form of complex I were observed in CAD. We observed a corresponding increase in glycolytic flux, indicated by a rise in pyruvate kinase and lactate dehydrogenase activity, indicating a compensatory increase in glycolysis for cellular energetics. Together, these results indicate a shift in mitochondrial metabolism from oxidative phosphorylation to glycolysis in human hearts subjects with CAD.

Author List

Ait-Aissa K, Blaszak SC, Beutner G, Tsaih SW, Morgan G, Santos JH, Flister MJ, Joyce DL, Camara AKS, Gutterman DD, Donato AJ, Porter GA Jr, Beyer AM

Authors

Andreas M. Beyer PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of Wisconsin
David D. Gutterman MD Sr Associate Director, Professor in the Medicine department at Medical College of Wisconsin
David L. Joyce MD Associate Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Coronary Artery Disease
DNA, Mitochondrial
Energy Metabolism
Female
Glycolysis
Heart
Humans
Male
Middle Aged
Mitochondria
NAD
Oxidation-Reduction
Oxidative Phosphorylation