Mitochondrial structure and function are not different between nonfailing donor and end-stage failing human hearts

Katherine M. Holzem, Kalyan C. Vinnakota, Vinod K. Ravikumar, Eli J. Madden, Gregory A. Ewald, Krikor Dikranian, Daniel A. Beard, Igor R. Efimov

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 LVisolated 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 mitochondrionwas increased.Analysis ofFAprocessing 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.

Original languageEnglish
Pages (from-to)2698-2707
Number of pages10
JournalFASEB Journal
Volume30
Issue number8
DOIs
StatePublished - Aug 2016

Keywords

  • Electron microscopy
  • Energy substrate
  • Lipid droplet
  • Oxidative respiration
  • Perilipin 5

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