A unique molecular basis for enzyme mistargeting in primary hyperoxaluria type 1

Clinica Chimica Acta; International Journal of Clinical Chemistry
J M Leiper, Christopher J Danpure

Abstract

The intermediary metabolic enzyme alanine:glyoxylate aminotransferase (AGT) is normally targeted to the peroxisomes in human liver cells. However, in a third of patients suffering from the autosomal recessive disease primary hyperoxaluria type 1 (PH1), AGT is mistargeted to the mitochondria. Such organelle-to-organelle mistargeting is without parallel in human genetic disease. AGT mistargeting results from the combination of a common Pro11-->Leu polymorphism and a rare Gly170-->Arg mutation. The former generates a functionally weak mitochondrial targeting sequence (MTS) while the latter, in combination with the former, increases the efficiency of this MTS by slowing the rate at which AGT dimerises. The fact that the intracellular compartmentation of AGT can be determined, at least in part, by its oligomeric status highlights the fundamental differences in the molecular requirements for protein import into two intracellular organelles--the peroxisomes and mitochondria.

References

Jan 1, 1990·Annual Review of Biochemistry·N Pfanner, W Neupert
Jan 1, 1988·Annual Review of Cell Biology·G Attardi, G Schatz
May 1, 1989·The Journal of Cell Biology·S J GouldS Subramani
Oct 1, 1988·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·P J CooperK M Guttridge
Jan 1, 1985·Annual Review of Cell Biology·P B Lazarow, Y Fujiki
Jun 1, 1995·Molecular Biology of the Cell·P A WaltonS Subramani
Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·J R GloverR A Rachubinski
Dec 1, 1994·The Journal of Cell Biology·J A McNew, J M Goodman
Jan 1, 1994·Journal of Inherited Metabolic Disease·C J DanpureJ Allsop
Dec 16, 1993·Biochimica Et Biophysica Acta·E MiddelkoopJ M Tager
Jan 1, 1995·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·C J Danpure

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Citations

Jun 1, 2000·Archives of Disease in Childhood·P Cochat, O Basmaison
Sep 29, 2006·Biochimica Et Biophysica Acta·Ida J van der Klei, Marten Veenhuis
Mar 30, 2010·Biochimica Et Biophysica Acta·M IslingerM Schrader

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