TY - JOUR
T1 - Mitochondrial structure and function are not different between nonfailing donor and end-stage failing human hearts
AU - Holzem, Katherine M.
AU - Vinnakota, Kalyan C.
AU - Ravikumar, Vinod K.
AU - Madden, Eli J.
AU - Ewald, Gregory A.
AU - Dikranian, Krikor
AU - Beard, Daniel A.
AU - Efimov, Igor R.
N1 - Publisher Copyright:
© FASEB.
PY - 2016/8
Y1 - 2016/8
N2 - 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.
AB - 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.
KW - Electron microscopy
KW - Energy substrate
KW - Lipid droplet
KW - Oxidative respiration
KW - Perilipin 5
UR - http://www.scopus.com/inward/record.url?scp=84980318156&partnerID=8YFLogxK
U2 - 10.1096/fj.201500118R
DO - 10.1096/fj.201500118R
M3 - Article
C2 - 27075244
AN - SCOPUS:84980318156
SN - 0892-6638
VL - 30
SP - 2698
EP - 2707
JO - FASEB Journal
JF - FASEB Journal
IS - 8
ER -