title: Mitochondrial structure and function are not different between nonfailing donor and end-stage failing human hearts.
abstract: During human heart failure, the balance of cardiac energy use switches from predominantly fatty acids (FAs) to glucose. We hypothesized that this substrate shift was the result of mitochondrial degeneration; therefore, we examined mitochondrial oxidation and ultrastructure in the failing human heart by using respirometry, transmission electron microscopy, and gene expression studies of demographically matched donor and failing human heart left ventricular (LV) tissues. Surprisingly, respiratory capacities for failing LV isolated mitochondria (n = 9) were not significantly diminished compared with donor LV isolated mitochondria (n = 7) for glycolysis (pyruvate + malate)- or FA (palmitoylcarnitine)-derived substrates, and mitochondrial densities, assessed via citrate synthase activity, were consistent between groups. Transmission electron microscopy images also showed no ultrastructural remodeling for failing vs. donor mitochondria; however, the fraction of lipid droplets (LDs) in direct contact with a mitochondrion was reduced, and the average distance between an LD and its nearest neighboring mitochondrion was increased. Analysis of FA processing gene expression between donor and failing LVs revealed 0.64-fold reduced transcript levels for the mitochondrial-LD tether, perilipin 5, in the failing myocardium (P = 0.003). Thus, reduced FA use in heart failure may result from improper delivery, potentially via decreased perilipin 5 expression and mitochondrial-LD tethering, and not from intrinsic mitochondrial dysfunction.-Holzem, K. M., Vinnakota, K. C., Ravikumar, V. K., Madden, E. J., Ewald, G. A., Dikranian, K., Beard, D. A., Efimov, I. R. Mitochondrial structure and function are not different between nonfailing donor and end-stage failing human hearts.
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA;
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Holzem
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA;
authors.forename: Kalyan C
authors.initials: KC
authors.lastname: Vinnakota
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA;
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Ravikumar
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA;
authors.forename: Eli J
authors.initials: EJ
authors.lastname: Madden
authors.affiliation: Washington University School of Medicine, St. Louis, Missouri, USA;
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Ewald
authors.affiliation: Washington University School of Medicine, St. Louis, Missouri, USA;
authors.forename: Krikor
authors.initials: K
authors.lastname: Dikranian
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA;
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Beard
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA; George Washington University, Washington, D.C., USA efimov@gwu.edu.
authors.forename: Igor R
authors.initials: IR
authors.lastname: Efimov
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006333:Heart Failure / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000473:pathology* / Q000502:physiology* / Q000648:ultrastructure; D014019:Tissue Donors
keywords: electron microscopy; energy substrate; lipid droplet; oxidative respiration; perilipin 5