Loss of STING in parkin mutant flies suppresses muscle defects and mitochondria damage.

Publication date: Jul 13, 2023

The early pathogenesis and underlying molecular causes of motor neuron degeneration in Parkinson’s Disease (PD) remains unresolved. In the model organism Drosophila melanogaster, loss of the early-onset PD gene parkin (the ortholog of human PRKN) results in impaired climbing ability, damage to the indirect flight muscles, and mitochondrial fragmentation with swelling. These stressed mitochondria have been proposed to activate innate immune pathways through release of damage associated molecular patterns (DAMPs). Parkin-mediated mitophagy is hypothesized to suppress mitochondrial damage and subsequent activation of the cGAS/STING innate immunity pathway, but the relevance of this interaction in the fly remains unresolved. Using a combination of genetics, immunoassays, and RNA sequencing, we investigated a potential role for STING in the onset of parkin-null phenotypes. Our findings demonstrate that loss of Drosophila STING in flies rescues the thorax muscle defects and the climbing ability of parkin-/- mutants. Loss of STING also suppresses the disrupted mitochondrial morphology in parkin-/- flight muscles, suggesting unexpected feedback of STING on mitochondria integrity or activation of a compensatory mitochondrial pathway. In the animals lacking both parkin and sting, PINK1 is activated and cell death pathways are suppressed. These findings support a unique, non-canonical role for Drosophila STING in the cellular and organismal response to mitochondria stress.

Open Access PDF

Concepts Keywords
Death Damage
Drosophila Defects
Immunoassays Drosophila
Mutants Early
Parkinson Flies


Type Source Name
drug DRUGBANK Trihexyphenidyl
drug DRUGBANK Profenamine
disease MESH defects
disease MESH pathogenesis
disease MESH neuron degeneration
pathway REACTOME Release
pathway KEGG Mitophagy
disease MESH Neurological Disorders
disease MESH Stroke
drug DRUGBANK Famotidine
disease MESH death
disease MESH Neurodegenerative diseases
disease MESH inflammation
pathway KEGG Autophagy
disease MESH oxidative stress
drug DRUGBANK Coenzyme M
pathway KEGG Apoptosis
disease MESH posture
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK Trestolone
drug DRUGBANK Sodium lauryl sulfate
disease MESH synthetic lethality
drug DRUGBANK Imidacloprid
disease MESH infection
drug DRUGBANK Glutathione
disease MESH starvation
drug DRUGBANK Cinacalcet
drug DRUGBANK Water
drug DRUGBANK Gold
drug DRUGBANK Esomeprazole
drug DRUGBANK Serine
drug DRUGBANK Phosphate ion
drug DRUGBANK Tromethamine
drug DRUGBANK Ilex paraguariensis leaf
drug DRUGBANK Edetic Acid
drug DRUGBANK Dodecyl sulfate
drug DRUGBANK Human Serum Albumin
drug DRUGBANK Methylergometrine
drug DRUGBANK Indoleacetic acid
drug DRUGBANK Zoledronic acid
drug DRUGBANK Monopotassium phosphate
drug DRUGBANK Sodium Citrate
drug DRUGBANK Trimebutine

Original Article

(Visited 1 times, 1 visits today)

Leave a Comment

Your email address will not be published. Required fields are marked *