Eira da Costa 2013 Abstract MiP2013
Eira da Costa AC (2013) Drosophila Trap1 protects against mitochondrial dysfunction in a PINK1/parkin model of Parkinsonβs disease. Mitochondr Physiol Network 18.08. |
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MiP2013, Book of Abstracts Open Access
Eira da Costa AC (2013)
Event: MiPNet18.08_MiP2013
Mitochondrial dysfunction caused by protein aggregation has been shown to have an important role in neurological diseases, such as Parkinsonβs disease (PD). Mitochondria have evolved at least two levels of defense mechanisms that ensure their integrity and the viability of their host cell. First, molecular quality control, through the upregulation of mitochondrial chaperones and proteases, guarantees the clearance of damaged proteins. Second, organellar quality control ensures the clearance of defective mitochondria through their selective autophagy. Studies in Drosophila have highlighted mitochondrial dysfunction linked with the loss of the PTEN-induced putative kinase 1 (Pink1) as a mechanism of PD pathogenesis. The mitochondrial chaperone TNF receptor-associated protein 1 (Trap1) was recently reported to be a cellular substrate for the Pink1 kinase. We characterized Drosophila Trap1 null mutants and described the genetic analysis of Trap1 function with Pink1 and parkin. We showed that loss of Trap1 resulted in a decrease in mitochondrial function and increased sensitivity to stress, and that its upregulation in neurons of Pink1 mutant flies rescued mitochondrial impairment. Additionally, the expression of Trap1 was able to partially rescue mitochondrial impairment in parkin mutant flies; and conversely, expression of parkin rescued mitochondrial impairment in Trap1 mutants. We conclude that Trap1 works downstream of Pink1 and in parallel with parkin in Drosophila, and that enhancing its function may ameliorate mitochondrial dysfunction and rescue neurodegeneration in PD.
Labels: MiParea: Genetic knockout;overexpression Pathology: Neurodegenerative, Parkinson's Stress:Cell death Organism: Drosophila, Hexapods
MiP2013, S12
Affiliations and author contributions
Cell Death Regulation Laboratory, MRC Toxicology Unit, Leicester, UK. - Email: [email protected]