AJP - Endocrinology and Metabolism, Vol 239, Issue 1 51-E56, Copyright © 1980 by American Physiological Society
Mithcondrial glutamine permeability and renal ammonia production in metabolic acidosis
T. C. Welbourne and G. T. Bazer
These experiments were undertaken to determine the correspondence between
acidosis-induced in situ motochondrial glutamine uptake and the process by
which glutamine moves across the mitochondrial membrane. Feeding rats 1.5%
NH4Cl for 2 wk accelerated the in situ uptake rate from 0.12 +/- 0.08 to
1.89 +/- 0.28 mu mol/min or some 16-fold. To determine glutamine uptake
independent of its metabolic conversion, D-glutamine was employed. In
isolated mitochondria from non-acidotic rat kidneys, D-glutamine diffused
into 71 +/- 10% of the mitochondria water volume; in acidotic mitochondria
the diffusion volume increased to 127 +/- 16%. The reflection coefficients
(sigma) for a series of amides, including glutamine, were determined by
gravimetrically following volume decrements in increasing concentrations of
solute; D-glutamine's sigma fell from 1.05 +/- 0.08 to 0.50 +/- 0.06 in
acidotic rat kidney mitchondria, The permeability coefficients
corresponding to the measured sigma were 10(-7) cm/s and 10(-5) cm/s in
nonacidosis and acidosis, respectively. When viewed in situ proximal tubule
mitochondria undergo dramatic alterations during chronic acidosis. These
involved an enlargement in the mitochondria particularly in the basal
region of the cell and a reduction in number. Furthermore, numerous
autophagic vacuoles, containing mitochondria, appear in the basal region.
The findings are consistent availability that becomes activated during
acidosis as a consequence of mitochondrial glutamine permeability resulting
in increased ammoniagenesis and accelerated organelle turnover.
