Inorganic polyphosphate and energy metabolism in mammalian cells.
Inorganic polyphosphate (poly P) is a polymer made from as few as 10 to several hundred phosphate molecules linked by phosphoanhydride bonds similar to ATP. Poly P is ubiquitous in all mammalian organisms, where it plays multiple physiological roles. The metabolism of poly P in mammalian organisms is not well understood. We have examined the mechanism of poly P production and the role of this polymer in cell energy metabolism. Poly P levels in mitochondria and intact cells were estimated using a fluorescent molecular probe, 4',6-diamidino-2-phenylindole. Poly P levels were dependent on the metabolic state of the mitochondria. Poly P levels were increased by substrates of respiration and in turn reduced by mitochondrial inhibitor (rotenone) or an uncoupler (carbonyl cyanide p-trifluoromethoxyphenylhydrazone). Oligomycin, an inhibitor of mitochondrial ATP-synthase, blocked the production of poly P. Enzymatic depletion of poly P from cells significantly altered the rate of ATP metabolism. We propose the existence of a feedback mechanism where poly P production and cell energy metabolism regulate each other.
Pavlov
Evgeny
E
Departments of Physiology and Biophysics, Calgary, Alberta T2N 4N1, Canada.
Aschar-Sobbi
Roozbeh
R
Departments of Physiology and Biophysics, Calgary, Alberta T2N 4N1, Canada.
Campanella
Michelangelo
M
Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, United Kingdom; Consortium for Mitochondrial Research, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Turner
Raymond J
RJ
Biological Sciences, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Gómez-García
María R
MR
Department of Plant Biology, Carnegie Institution for Science, Stanford University, Stanford, California 94305.
Abramov
Andrey Y
AY
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom. Electronic address: a.abramov@ucl.ac.uk.
D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D004586:Electrophoresis; D004734:Energy Metabolism; D005456:Fluorescent Dyes / Q000494:pharmacology; D006868:Hydrolysis; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D009840:Oligomycins / Q000737:chemistry; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D011108:Polymers / Q000737:chemistry; D011122:Polyphosphates / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005456:Fluorescent Dyes; D009840:Oligomycins; D011108:Polymers; D011122:Polyphosphates; D000255:Adenosine Triphosphate