The STING pathway does not contribute to behavioural or mitochondrial phenotypes in Drosophila Pink1/parkin or mtDNA mutator models.
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Lee, J. J., Andreazza, S., & Whitworth, A. J. (2020). The STING pathway does not contribute to behavioural or mitochondrial phenotypes in Drosophila Pink1/parkin or mtDNA mutator models.. Scientific reports, 10 (1)https://doi.org/10.1038/s41598-020-59647-3
Mutations in PINK1 and Parkin/PRKN cause the degeneration of dopaminergic neurons in familial forms of Parkinson's disease but the precise pathogenic mechanisms are unknown. The PINK1/Parkin pathway has been described to play a central role in mitochondrial homeostasis by signalling the targeted destruction of damaged mitochondria, however, how disrupting this process leads to neuronal death was unclear until recently. An elegant study in mice revealed that the loss of Pink1 or Prkn coupled with an additional mitochondrial stress resulted in the aberrant activation of the innate immune signalling, mediated via the cGAS/STING pathway, causing degeneration of dopaminergic neurons and motor impairment. Genetic knockout of Sting was sufficient to completely prevent neurodegeneration and accompanying motor deficits. To determine whether Sting plays a conserved role in Pink1/parkin related pathology, we tested for genetic interactions between Sting and Pink1/parkin in Drosophila. Surprisingly, we found that loss of Sting, or its downstream effector Relish, was insufficient to suppress the behavioural deficits or mitochondria disruption in the Pink1/parkin mutants. Thus, we conclude that phenotypes associated with loss of Pink1/parkin are not universally due to aberrant activation of the STING pathway.
Medical Research Council (1804239)
RCUK | MRC | Medical Research Foundation (MC_UU_00015/6)
European Research Council (309742)
External DOI: https://doi.org/10.1038/s41598-020-59647-3
This record's URL: https://www.repository.cam.ac.uk/handle/1810/303576
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/