The Mitochondrial Chaperone Protein TRAP1 Mitigates α-Synuclein Toxicity

• DOI: 10.1371/journal.pgen.1002488
• Publication Date: 2012-02-02T21:43:49Z
• Authors: Erin K. Butler; Aaron Voigt; A. Kathrin Lutz; Jane P. Toegel; Ellen Gerhardt; Peter Karsten; Björn Falkenburger; Andrea Reinartz; Konstanze F. Wink...; Jörg B. Schulz
• Keywords: Chaperone (clinical); Mitochondrial toxicity

Overexpression or mutation of α-Synuclein is associated with protein aggregation and interferes a number cellular processes, including mitochondrial integrity function. We used whole-genome screen in the fruit fly Drosophila melanogaster to search for novel genetic modifiers human [A53T]α-Synuclein–induced neurotoxicity. Decreased expression chaperone tumor necrosis factor receptor protein-1 (TRAP1) was found enhance age-dependent loss head dopamine (DA) DA neuron resulting from [A53T]α-Synuclein expression. In addition, decreased TRAP1 [A53T]α-Synuclein–expressing flies resulted enhanced climbing ability sensitivity oxidative stress. able rescue these phenotypes. Similarly, overexpression rat primary cortical neurons rescued rotenone treatment. (non)neuronal cell lines, small interfering RNA directed against stress directly interfered function, as its reduced Complex I activity HEK293 cells. These effects were blocked by overexpression. Moreover, prevent alteration morphology caused SH-SY5Y results indicate that toxicity intimately connected dysfunction reduction lines can be achieved using TRAP1. Interestingly, has previously been shown phosphorylated serine/threonine kinase PINK1, thus providing potential link PINK1 via α-Synuclein.