Matching ATP supply and demand in mammalian heart: In vivo, in vitro, and in silico perspectives

Yael Yaniv, Magdalena Juhaszova, H. Bradley Nuss, Su Wang, Dmitry B. Zorov, Edward G. Lakatta, Steven J. Sollott

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Although the heart rapidly adapts cardiac output to match the body's circulatory demands, the regulatory mechanisms ensuring that sufficient ATP is available to perform the required cardiac work are not completely understood. Two mechanisms have been suggested to serve as key regulators: (1) ADP and Pi concentrations - ATP utilizationhydrolysis in the cytosol increases ADP and Pi fluxes to mitochondria and hence the amount of available substrates for ATP production increases; and (2) Ca2+ concentration - ATP utilizationhydrolysis is coupled to changes in free cytosolic calcium and mitochondrial calcium, the latter controlling Ca2+-dependent activation of mitochondrial enzymes taking part in ATP production. Here we discuss the evolving perspectives of each of the putative regulatory mechanisms and the precise molecular targets (dehydrogenase enzymes, ATP synthase) based on existing experimental and theoretical evidence. The data synthesis can generate novel hypotheses and experimental designs to solve the ongoing enigma of energy supply-demand matching in the heart.

Original languageEnglish (US)
Title of host publicationAnalysis of Cardiac Development
Subtitle of host publicationFrom Embryo to Old Age
PublisherBlackwell Publishing Inc.
Pages133-142
Number of pages10
ISBN (Print)9781573317474
DOIs
StatePublished - Feb 2010
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1188
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • ATP synthase
  • Bioenergetics
  • Mitochondria
  • Respiration

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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