Aiyar RS~Steinmetz LM, 2014

Pubmed ID 25519239
Title Mitochondrial protein sorting as a therapeutic target for ATP synthase disorders.
Authors Raeka S Aiyar, Maria Bohnert, Stéphane Duvezin-Caubet, Cécile Voisset, Julien Gagneur, Emilie S Fritsch, Elodie Couplan, Karina von der Malsburg, Charlotta Funaya, Flavie Soubigou, Florence Courtin, Sundari Suresh, Roza Kucharczyk, Justine Evrard, Claude Antony, Robert P St Onge, Marc Blondel, Jean-Paul di Rago, Martin van der Laan, Lars M Steinmetz
Abstract Mitochondrial diseases are systemic, prevalent and often fatal; yet treatments remain scarce. Identifying molecular intervention points that can be therapeutically targeted remains a major challenge, which we confronted via a screening assay we developed. Using yeast models of mitochondrial ATP synthase disorders, we screened a drug repurposing library, and applied genomic and biochemical techniques to identify pathways of interest. Here we demonstrate that modulating the sorting of nuclear-encoded proteins into mitochondria, mediated by the TIM23 complex, proves therapeutic in both yeast and patient-derived cells exhibiting ATP synthase deficiency. Targeting TIM23-dependent protein sorting improves an array of phenotypes associated with ATP synthase disorders, including biogenesis and activity of the oxidative phosphorylation machinery. Our study establishes mitochondrial protein sorting as an intervention point for ATP synthase disorders, and because of the central role of this pathway in mitochondrial biogenesis, it holds broad value for the treatment of mitochondrial diseases.
Citation Nat Commun 2014; 5:5585

Datasets

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Paper Phenotype Condition Medium Collection Tested mutants Data Details
Aiyar RS~Steinmetz LM, 2014 growth (pooled culture) Sodium pyrithione [8.35 uM] YPD hom 4,765 Quantitative
Aiyar RS~Steinmetz LM, 2014 growth (pooled culture) Sodium pyrithione [8.35 uM] YPD het 1,132 Quantitative

Curation history

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