Dr Payam Gammage - Mitochondrial Oncogenetics


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Mitochondria are a cellular nexus, performing numerous signalling, biosynthetic and bioenergetic functions. In humans, mitochondria are composed of ~1200 proteins, the vast majority encoded in nuclear DNA, with a minor subset encoded in the spatially and heritably separate mitochondrial DNA (mtDNA).

The human mitochondrial genome is a genetically compact, circular, double-stranded DNA molecule of 16.5 kb, typically present at between 100 and 10,000 copies per cell on a cell type-specific basis. Encoded exclusively in mtDNA are subunits of the mitochondrial respiratory chain and ATP synthase, required for functional oxidative phosphorylation, and all RNA components necessary for their translation by mitochondrial ribosomes.

Mutations, deletions and rearrangements of mtDNA are a known source of hereditary metabolic disease in humans, causing a broad spectrum of pathology underpinned by mitochondrial dysfunction. Mutations of mtDNA are also found in approximately 60% of all solid tumours, often at levels that would result in profound mitochondrial dysfunction.

Mitochondrial dysregulation and dysfunction, particularly a switch from oxidative to glycolytic metabolism, is often observed in cancer. Our research focuses on determining the role of mitochondrial genetics and gene expression in human cancer.

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