AJP - Heart and Circulatory Physiology, Vol 247, Issue 1 25-H34, Copyright © 1984 by American Physiological Society
Protective role of adenine nucleotide translocase in O2-deficient hearts
S. V. Pande, T. Goswami and R. Parvin
At subsaturating concentrations of palmitoyl-CoA, the carnitine-dependent
oxidation of the palmitoyl portion by uncoupled rat heart mitochondria was
stimulated by ADP or ATP. This effect was traced to the prevention of
acyl-CoA binding to adenine nucleotide translocase and the consequent
sparing of acyl-CoA for acylcarnitine formation. Palmitoyl-CoA oxidation
was stimulated by ITP also although ITP served neither as a transportable
substrate nor as an inhibitor of ADP transport. ITP and other
nontransportable nucleoside di(tri)phosphates prevented octanoyl-CoA
binding to mitochondria. ITP was bound to mitochondria, and this binding
was reversed by ADP, octanoyl-CoA, and carboxyatractyloside. Thus, besides
a substrate site, there is a site on the translocase that binds nucleoside
di(tri)phosphates, CoA and its esters, and atractylosides; inhibition of
the translocase results, however, only from the binding of CoA esters of
fatty acids and of atractylosides. We suggest that in O2-deficient hearts,
when nucleotides decline and fatty acyl-CoA rises, the binding of the
latter to the translocase becomes operational to slow fatty acylcarnitine
production. By retarding the rise in amphipathic burden, this mechanism
could protect heart against irreversible damage during brief periods of
ischemia or hypoxia.
