Response of the mitochondrial proteome of rat renal proximal convoluted tubules to chronic metabolic acidosis

American Journal of Physiology. Renal Physiology
Dana M FreundNorman P Curthoys

Abstract

Metabolic acidosis is a common clinical condition that is caused by a decrease in blood pH and bicarbonate concentration. Increased extraction and mitochondrial catabolism of plasma glutamine within the renal proximal convoluted tubule generates ammonium and bicarbonate ions that facilitate the excretion of acid and partially restore acid-base balance. Previous studies identified only a few mitochondrial proteins, including two key enzymes of glutamine metabolism, which are increased during chronic acidosis. A workflow was developed to characterize the mitochondrial proteome of the proximal convoluted tubule. Based upon the increase in specific activity of cytochrome c oxidase, the isolated mitochondria were enriched eightfold. Two-dimensional liquid chromatography coupled with mass spectrometry was utilized to compare mitochondrial-enriched samples from control and chronic acidotic rats. Proteomic analysis identified 901 proteins in the control and acidotic samples. Further analysis identified 37 peptides that contain an N-ε-acetyl-lysine; of these, 22 are novel sites. Spectral counting analysis revealed 33 proteins that are significantly altered in abundance in response to chronic metabolic acidosis. Western blot analysis was...Continue Reading

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Related Concepts

Acetylation
Metabolic Acidosis
Ammonium Chloride
Cytochrome c Oxidase Subunit VIa
Hypertrophy
Kidney Tubules, Proximal
Lysine Hydrochloride
Mitochondria
Western Blot
Rats, Holtzman

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