Mitochondria are intracellular organelles that function as the powerhouses of all cells producing more than 90% of the total energy needed to sustain life, growth and development. Humans have hundreds of mitochondria in every cell of their body that make up about 20% of the cell volume. Defects in mitochondria may result in more than 50 different human diseases including type 2 diabetes, Parkinson's disease, Alzheimer's disease, atherosclerotic heart disease, stroke, and cancer. In the US, the incidence of mitochondrial disease is 1 in 4,000 births. They are usually progressive diseases and may affect the brain, nerves, muscles, heart, liver eventually leading to organ failure and death. To date there is no cure for mitochondrial diseases, although certain treatments exist.

Mitochondria biogenesis is not a simple task for the cell. These tiny organelles (the size of a bacterium) are made from about 1500 different proteins. From these proteins only a handful are encoded by mitochondrial DNA (the only extranuclear DNA in human cells); the vast majority are synthesised in the cytosol and are then imported into the organelle. Therefore the protein import process is crucial for mitochondria biogenesis.

The new research identified a novel mechanism necessary for targeting and trapping proteins inside mitochondria. The IMBB team (the PhD student Dionisia Sideris and the research technician Nitsa Katrakili headed by University of Crete Associate Professor and IMBB group leader Dr Kostas Tokatlidis) in collaboration with the team of Ivano Bertini at the University of Florence,combined genetic and biochemical experiments with structural studies. They discovered that Mia40, a protein found in every eukaryotic organism including humans, introduces chemical (disulfide) bridges into proteins targeted to the mitochondrial intermembrane space. In this way it 'locks' them in a three-dimensional conformation inside mitochondria where they are now biologically active. This novel process of oxidative protein folding affects several important proteins of the mitochondrial intermembrane space that function in respiration, transport of metabolite carriers etc. This work is anticipated to open new avenues for targeted therapeutic interventions in a whole variety of mitochondrial diseases, ageing and cancer in humans.

For more information please contact:

Dr. Kostas Tokatlidis, Associate Professor/IMBB Group Leader (tel: 30 2810 391136, email: tokatlid@imbb.forth.gr)
Prof. Ivano Bertini (CERM, University of Florence, Italy; bertini@cerm.unifi.it)

Relevant URL:

http://www.imbb.forth.gr/people/tokatlidis
http://www.nature.com/nsmb/journal/v16/n2/pdf/nsmb.1553.pdf
http://www.nature.com/nsmb/journal/v16/n2/index.html