Mitochondrial Oxidative Phosphorylation defect in the Heart of Subjects with Coronary Artery Disease

Karima Ait-Aissa; Scott C Blaszak; Gisela Beutner; Shirng-Wern Tsaih; Garrett Morgan; Janine H Santos; Michael J Flister; David L Joyce; Amadou K S Camara; David D Gutterman; Anthony J Donato; George A Porter Jr; Andreas M Beyer

doi:10.1038/s41598-019-43761-y

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Mitochondrial Oxidative Phosphorylation defect in the Heart of Subjects with Coronary Artery Disease

Journal article

Open access

Peer reviewed

Mitochondrial Oxidative Phosphorylation defect in the Heart of Subjects with Coronary Artery Disease

Karima Ait-Aissa, Scott C Blaszak, Gisela Beutner, Shirng-Wern Tsaih, Garrett Morgan, Janine H Santos, Michael J Flister, David L Joyce, Amadou K S Camara, David D Gutterman, …

Scientific reports, Vol.9(1), pp.7623-7623

05/20/2019

DOI: 10.1038/s41598-019-43761-y

PMCID: PMC6527853

PMID: 31110224

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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 ( DNA), 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 DNA 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.

Adenosine Triphosphate - metabolism

Coronary Artery Disease - metabolism

DNA, Mitochondrial - metabolism

Energy Metabolism - physiology

Female

Glycolysis - physiology

Heart - physiopathology

Humans

Male

Middle Aged

Mitochondria - metabolism

NAD - metabolism

Oxidation-Reduction

Oxidative Phosphorylation

Details

Title: Subtitle: Mitochondrial Oxidative Phosphorylation defect in the Heart of Subjects with Coronary Artery Disease
Creators: Karima Ait-Aissa - Medical College of Wisconsin
Scott C Blaszak - Medical College of Wisconsin
Gisela Beutner - University of Rochester Medical Center
Shirng-Wern Tsaih - Medical College of Wisconsin
Garrett Morgan - University of Utah
Janine H Santos - Genome Integrity and Structural Biology Laboratory, NIHEHS, Raleigh-Durham, NC, USA.
Michael J Flister - Medical College of Wisconsin
David L Joyce - Medical College of Wisconsin
Amadou K S Camara - Medical College of Wisconsin
David D Gutterman - Medical College of Wisconsin
Anthony J Donato - University of Utah
George A Porter Jr - University of Rochester Medical Center
Andreas M Beyer - Medical College of Wisconsin
Resource Type: Journal article
Publication Details: Scientific reports, Vol.9(1), pp.7623-7623
DOI: 10.1038/s41598-019-43761-y
PMID: 31110224
PMCID: PMC6527853
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Grant note: R01 HL113612 / NHLBI NIH HHS R21 OD018306 / NIH HHS R01 HL133029 / NHLBI NIH HHS
Language: English
Date published: 05/20/2019
Academic Unit: Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984359846502771

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