An isoform of hPANK2, deficient in pantothenate kinase-associated neurodegeneration, localizes to mitochondria

Konstanze Hörtnagel, Holger Prokisch, Thomas Meitinger

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Mutations in the human PANK2 gene have been shown to occur in autosomal-recessive pantothenate kinase-associated neurodegeneration, a syndrome originally described by Hallervorden and Spatz. The kinase catalyses the first and rate-limiting step in the biosynthesis of coenzyme A, a key molecule in energy metabolism. We have determined the exon-intron structure of the hPANK2 gene and identified two alternatively used first exons. The resulting transcripts encode distinct isoforms of hPANK2, one of which carries an N-terminal extension with a predicted mitochondrial targeting signal. An in vitro import assay and in vivo immunolocalization experiments demonstrate a mitochondrial localization of this isoform. We conclude that the symptoms observed in pantothenate kinase-associated neurodegeneration are caused by a deficiency of the mitochondrial isoform and postulate the existence of a complete intramitochondrial pathway for de novo synthesis of coenzyme A.

Original languageEnglish
Pages (from-to)321-327
Number of pages7
JournalHuman Molecular Genetics
Volume12
Issue number3
DOIs
StatePublished - 1 Feb 2003

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