The Atypical Cadherin Fat Directly Regulates Mitochondrial Function and Metabolic State

Researchers at the University of Toronto/Lunenfeld-Tanenbaum Research Institute (Canada) report a discovery with implications for diseases linked to mitochondria, dysfunction of which may be linked to illnesses such as Type 2 diabetes, Parkinson’s disease, heart disease, stroke, and Alzheimer’s disease.  The group focuses on mutations in the fat (ft) gene. The protein product of this gene, called ‘Fat’, acts at the cell membrane to promote adhesion and communication between cells. Mutations in ft can cause cells to overgrow and become tumors. This occurs partially through the Hippo pathway, a pathway that is frequently activated in cancers such as liver, breast, ovarian and sarcomas.   The team observed that a piece of the Fat protein is actually processed and delivered into the mitochondria where it influences the energy status of the cell. Importantly, when this particular component is missing, the energy generating pipeline inside mitochondria become destabilized, leading to loss of energy production.  The study authors submit that: “Defects in mitochondrial activity in ft mutants are independent of Hippo and [planar cell polarity] signaling and are reminiscent of the Warburg effect.”