Metabolic rewiring of mitochondria in cancer

Mitochondria are versatile metabolic hubs with central functions in cellular energy metabolism. Mitochondrial deficiencies occur with age and are associated with pleiotropic diseases affecting primarily muscle tissues and the brain. Our lab focuses on cellular mechanisms that allow adaptation of mitochondrial activities to different physiological demands and their disturbance during ageing and in disease. We found that hypoxic and starved cells proteolytically rewire their mitochondrial proteome upon shift from OXPHOS to glycolytic growth. Mitochondrial reshaping is mediated by the protease YME1L and supports the growth of pancreatic ductal adenocarcinoma (PDAC) cells as spheroids or xenografts. Similar changes to the mitochondrial proteome occur in the tumor tissues of patients with PDAC but not with hepatocellular carcinomas, suggesting the YME1L is relevant to the pathophysiology of PDAC. Current experiments using mouse models and proteomic as well as metabolomic approaches examine how YME1L mediated mitochondrial reshaping controls the cellular metabolism and the growth of tumor cells.