31P NMR measurement of mitochondrial uncoupling in isolated rat hearts

P. B. Kingsley-Hickman, E. Y. Sako, K. Ugurbil, A. H.L. From, J. E. Foker

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46 Scopus citations

Abstract

Mitochondrial uncoupling is often invoked as a mechanism underlying cellular dysfunction; however, it has not been possible to study this phenomenon directly in intact cells and tissues. In this paper, we report direct evaluation of mitochondrial uncoupling in the intact myocardium using 31P NMR magnetization transfer techniques. Langendorff perfused rat hearts were exposed to either a known uncoupler, 2,4-dinitrophenol (DNP), or a potential uncoupler, octanoate. Both DNP and octanoate decreases mechanical function as measured by the rate pressure product and caused an increase in the oxygen consumption rate (MVO2); with DNP this increase in MVO2 was dose-dependent. The ATP synthesis rate measured by 31P NMR, however, was not elevated commensurately with MVO2; instead, the P/O ratio declined. In contrast, the linear relationship between the ATP synthesis rate and rate pressure product was not altered by the uncoupling agents. These data demonstrate that 1) 31P NMR magnetization transfer can be utilized to measure uncoupling of oxidative phosphorylation in intact organs, 2) octanoate does not induce excess ATP utilization in the intact heart, and 3) high levels of octanoate induce mitochondrial uncoupling in the intact myocardium; and this may, in part, be the cause of the toxic effects associated with fatty acid exposure.

Original languageEnglish (US)
Pages (from-to)1545-1550
Number of pages6
JournalJournal of Biological Chemistry
Volume265
Issue number3
StatePublished - 1990
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Kingsley-Hickman, P. B., Sako, E. Y., Ugurbil, K., From, A. H. L., & Foker, J. E. (1990). 31P NMR measurement of mitochondrial uncoupling in isolated rat hearts. Journal of Biological Chemistry, 265(3), 1545-1550.