Polyalanine tracts directly induce the release of cytochrome c, independently of the mitochondrial permeability transition pore, leading to apoptosis

Kazuya Toriumi, Yoko Oma, Ai Mimoto, Eugene Futai, Noboru Sasagawa, Boris Turk, Shoichi Ishiura

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

In recent years, several novel types of disorder caused by the expansion of triplet repeats in specific genes have been characterized; in the "polyalanine diseases", these expanded repeats result in proteins with aberrantly elongated polyalanine tracts. In this study, we fused expanded polyalanine tracts to yellow fluorescent protein to examine their physical interaction with mitochondria. Tracts containing more than 23 alanine repeats were found to physically associate with mitochondria, strongly suggesting that an interaction between polyalanine tracts and mitochondria is a contributing factor in the pathology of polyalanine diseases. Furthermore, in in vitro experiments, polyalanine tracts induced release of cytochrome c from mitochondria and caspase-3 activation, independently of the mitochondrial permeability transition pore. These results suggest that oligomerized polyalanine tracts might induce the rupture of the mitochondrial membrane, the subsequent release of cytochrome c, and apoptosis. This novel mechanism for polyalanine tract cytotoxicity might be common to the pathogenesis of all polyalanine diseases. Further investigation of this mechanism might aid the development of therapies for these diseases.

Original languageEnglish
Pages (from-to)751-757
Number of pages7
JournalGenes to Cells
Volume14
Issue number6
DOIs
Publication statusPublished - 2009 Jun 15
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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