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(Received for publication, August 20, 1996)
From the To maintain ATP constant in the cell,
mitochondria must sense cellular ATP utilization and transduce this
demand to F0-F1-ATPase. In spite of a
considerable research effort over the past three decades, no
combination of signal(s) and kinetic function has emerged with the
power to explain ATP homeostasis in all mammalian cells. We studied
this signal transduction problem in intact human muscle using
31P NMR spectroscopy. We find that the apparent kinetic
order of the transduction function of the signal cytosolic ADP
concentration ([ADP]) is at least second order and not first order as
has been assumed. We show that amplified mitochondrial
sensitivity to cytosolic [ADP] harmonizes with in vitro
kinetics of [ADP] stimulation of respiration and explains ATP
homeostasis also in mouse liver and canine heart. This result may well
be generalizable to all mammalian cells.
Volume 271, Number 45,
Issue of November 8, 1996
pp. 27995-27998
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
COMMUNICATION:
,
,
and**
NMR Research Laboratory, Department of
Radiology, University of Washington School of Medicine, Seattle,
Washington 98195, the ¶ Department of Microbial Physiology,
Faculty of Biology, Free University, NL-1081 HV Amsterdam, the
Netherlands, the 
E. C. Slater Institute, Biocenter, University
of Amsterdam, NL-1018 TV Amsterdam, the Netherlands, the ** Department
of Physiology and Biophysics, University of Washington School of
Medicine, Seattle, Washington 98195, and the
Center for Bioengineering, University of
Washington School of Medicine, Seattle, Washington 98185
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