Expression of polyalanine stretches induces mitochondrial dysfunction

Journal of Neuroscience Research
Kazuya ToriumiShoichi Ishiura

Abstract

In recent years, several novel types of disorders have been characterized, including what have been termed polyalanine diseases, in which patients have expanded triplet repeats in specific genes, resulting in the translation of aberrantly elongated polyalanine stretches. In this study, we showed that yellow fluorescent protein (YFP)-fused elongated polyalanine stretches localized exclusively to the cytoplasm and formed aggregates. Additionally, the polyalanine stretches themselves were toxic. We sought to identify proteins that bound directly to the polyalanine stretches, as factors that might be involved in triggering cell death. Many mitochondrial proteins were identified as polyalanine-binding proteins. We showed that one of the identified proteins, succinate dehydrogenase subunit A, was decreased in the mitochondria of cells expressing polyalanine stretches; as a result, succinate oxidative activity was decreased. Furthermore, the polyalanine stretches also associated directly with mitochondria. This suggests that polya-lanine stretches might directly induce cell death. Additionally, the mitochondrial membrane potential was reduced in cells expressing polyalanine stretches. We propose a novel mechanism by which polyalanine ...Continue Reading

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Citations

Jul 26, 2014·Biomolecules·Siobhan Toal, Reinhard Schweitzer-Stenner
Jun 3, 2009·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kazuya ToriumiShoichi Ishiura
Mar 21, 2009·Journal of Neuroscience Research·Jun NojimaShoichi Ishiura
Aug 18, 2010·Physical Chemistry Chemical Physics : PCCP·Lin NiuChen Wang
Sep 1, 2011·Molecular BioSystems·Reinhard Schweitzer-Stenner
Mar 22, 2019·Laboratory Investigation; a Journal of Technical Methods and Pathology·Tsukasa DokiYukio Ando
May 8, 2009·The Journal of Physical Chemistry. B·Achraf KouzayhaFrançoise Besson
Jun 17, 2021·The Journal of Physical Chemistry. B·Reinhard Schweitzer-Stenner, Nicolas J Alvarez

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