Mitochondria are a cellular organelle best known as producers of energy through oxidative phosphorylation. To produce energy, a proton-gradient needs to be established over the mitochondrial double-membrane. This fundamental process of proton-pumping within the mitochondrion is a defining feature of eukaryotic (higher) organisms and essential to cell growth. Mitochondrial dysfunction is associated with diseases ranging from neurodegeneration to cancer and no curative therapies for primary mitochondrial diseases exist. This project capitalises on an extra-mitochondrial pathway identified by genome-wide CRISPR/Cas9 screening alleviating mitochondrial dysfunction by increasing the mitochondrial membrane potential. Our primary data shows this pathway restores cell growth in primary cell lines from mitochondrial patients. Here we aim to use multiple patient-relevant models of mitochondrial disease to further investigate this pathway for its therapeutic potential.

2025

2029