dictyNews

Electronic Edition

Volume 46, number 30

October 30, 2020



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Abstracts

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Fernando, S.; Allan, C.Y.; Mroczek, K.; Pearce, X.; Sanislav, O.; 

Fisher, P.R.; Annesley, S.J. 



Cytotoxicity and Mitochondrial Dysregulation Caused by α-Synuclein 

in Dictyostelium discoideum. 





 Cells 2020, 9, 2289



Alpha synuclein has been linked to both sporadic and familial 

forms of Parkinson’s disease (PD) and is the most abundant protein 

in Lewy bodies a hallmark of Parkinson’s disease. The function of 

this protein and the molecular mechanisms underlying its toxicity 

are still unclear, but many studies have suggested that the 

mechanism of α-synuclein toxicity involves alterations to 

mitochondrial function. Here we expressed human α-synuclein and 

two PD-causing α-synuclein mutant proteins (with a point mutation, 

A53T, and a C-terminal 20 amino acid truncation) in the eukaryotic 

model Dictyostelium discoideum. Mitochondrial disease has been 

well studied in D. discoideum and, unlike in mammals, 

mitochondrial dysfunction results in a clear set of defective 

phenotypes. These defective phenotypes are caused by the chronic 

hyperactivation of the cellular energy sensor, AMP-activated 

protein kinase (AMPK). Expression of α-synuclein wild type and 

mutant forms was toxic to the cells and mitochondrial function was 

dysregulated. Some but not all of the defective phenotypes could 

be rescued by down regulation of AMPK revealing both AMPK-

dependent and -independent mechanisms. Importantly, we also 

show that the C-terminus of α-synuclein is required and sufficient 

for the localisation of the protein to the cell cortex in D. discoideum.





submitted by: Sarah Annesley [[log in to unmask]]

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[End dictyNews, volume 46, number 30]