Project 445205

All cells in the body require chemical energy to carry out their normal physiological functions. The majority of this energy is packaged as a compound called ATP and is produced by the oxidation of carbohydrate and fat in a biochemical process called oxidative phosphorylation. This process takes place in a compartment of the cell called the mitochondrion, and is carried out by several large protein complexes that constitute the mitochondrial respiratory chain. Respiratory chain dysfunction interferes with the normal supply of energy, and this produces a wide variety of different diseases, such as neurodegenerative and heart disease, the nature and severity of which depend on the exact genetic defect. The genetics of respiratory chain diseases is complicated by the fact that some components of the system are encoded in nuclear genes, others in a small genome that is contained within the mitochondria themselves. Mitochondria also rely on intimate contacts with other organelles in the cell, most notably a structure called the endoplasmic reticulum, which, among other things, supplies mitochondria with the lipids required for mitochondrial growth and division, and acts as a reservoir for calcium, which in part regulates mitochondrial metabolism. Several neurological diseases result from disturbances in the contacts between mitochondria and the ER. We have identified mutations in a gene coding protein of the mitochondrial metabolite carrier family, that seems to be involved in communication between the mitochondrial outer membrane and the endoplasmic reticulum, which result in an astonishingly large spectrum of neurological diseases and this project is aimed at investigating its precise molecular functions in healthy cells and in cells from patients with mitochondrial disease.