Journal article

AN AMINO-ACID SUBSTITUTION IN THE PYRUVATE-DEHYDROGENASE E1-ALPHA GENE, AFFECTING MITOCHONDRIAL IMPORT OF THE PRECURSOR PROTEIN

F TAKAKUBO, P CARTWRIGHT, N HOOGENRAAD, DR THORBURN, F COLLINS, T LITHGOW, HHM DAHL

AMERICAN JOURNAL OF HUMAN GENETICS | CELL PRESS | Published : 1995

Abstract

A mutation in the mitochondrial targeting sequence was characterized in a male patient with X chromosome-linked pyruvate dehydrogenase E1 alpha deficiency. The mutation was a base substitution of G by C at nucleotide 134 in the mitochondrial targeting sequence of the PDHA1 gene, resulting in an arginine-to-proline substitution at codon 10 (R10P). Pyruvate dehydrogenase activity in cultured skin fibroblasts was 28% of the control value, and immunoblot analysis revealed a decreased level of pyruvate dehydrogenase E1 alpha immunoreactivity. Chimeric constructs in which the normal and mutant pyruvate dehydrogenase E1 alpha targeting sequences were attached to the mitochondrial matrix protein orn..

View full abstract