Mass spectrometry analyses of normal and polyglutamine expanded ataxin-3 reveal novel interaction partners involved in mitochondrial function

• DOI: 10.1016/j.neuint.2017.10.013
• Publication Date: 2017-10-27T07:00:20Z
• Authors: Line V. Kristensen; Felix S. Oppermann; Matthias J. Rauen; Karina Fog; Thorsten Schmidt; Jana Schmidt; Tina Harmuth; Rasmus Hartmann-P...; Kenneth Thirstrup
• Keywords: 0301 basic medicine; Mice, Transgenic; Machado-Joseph Disease; Mass Spectrometry; Mitochondria; Mice; 03 medical and health sciences; HEK293 Cells; Journal Article; Animals; Humans; Protein Interaction Maps; Ataxin-3; Peptides

Deubiquitinating enzymes (DUBs) play important roles in a variety of cellular processes, including regulation of protein homeostasis. The DUB ataxin-3 is an enzyme implicated in protein quality control mechanisms. In the neurodegenerative disease spinocerebellar ataxia type 3 (SCA3), ataxin-3 contains an expanded polyglutamine (polyQ) stretch that leads to aggregation of the protein and neuronal dysfunction. Increasing the understanding of ataxin-3 protein interaction partners could help to elucidate disease mechanisms. Hence, we analyzed the repertoire of proteins interacting with normal and polyQ expanded ataxin-3 by mass spectrometry. This showed that both normal and polyQ expanded ataxin-3 interacted with components of the protein quality control system and mitochondria. Five proteins showed increased interaction with polyQ expanded ataxin-3 relative to normal and three of these were mitochondrial proteins. The analyses underline the role of ataxin-3 in ubiquitin biology and point towards a role in mitochondrial biology.