MPV17 IS A GENE RESPONSIBLE FOR THE MITOCHONDRIAL DNA DEPLETION SYNDROME

A new gene responsible for the hepatocerebral form of the Mitochondrial DNA Depletion Syndrome (MDDS) has been discovered by Antonella Spinazzola, researcher of Massimo Zeviani Laboratory. The article was published on Nature Genetics. Individuals with this form of MDDS, an autosomal recessive disorder, have early progressive liver failure and neurologic abnormalities, hypoglycemia, and increased lactate in body fluids. They usually die before 1 years of age. The work was based on collection of families that have been used for a genome wide screening. In collaboration with Professor Paolo Gasparini of the Trieste University, a region on chromosome 2 was identified as responsible for the disease. By using a bioinformatics integrated approach, MPV17 was identified as the gene responsible for the disease and mutations have been found in affected patients. MPV17 codes for a mitochondrial inner membrane protein, and its absence or malfunction causes energy production failure and mtDNA depletion, but its role in the pathogenesis of the disease has not been elucidated jet. The next step will be to clarify the molecular, cellular and physiopathological mechanisms of MPV17 alterations with the aim of identifying effective treatments.

MITOCHONDRIA ARE OXYGEN SIGNS

Understanding how cells sense and adapt to changes in oxygen availability is important because many diseases such as myocardial infarction, cancer, and strokes are characterized by impaired tissue oxygenation. Over the years, there have been reports as to the importance of mitochondria, as well as reactive oxygen species (ROS), with respect to oxygen sensing. Recently, three papers on Cell Metabolism have strenghtened that ROS produced by mitochondria under hypoxic conditions play an important rule in this process. ROS are required for the normal induction of HIF (hypoxia-inducible factor), which is a master regulator of oxygen-sensitive gene expression, by low oxygen. Valeria Tiranti and Massimo Zeviani are co-authors in the work of Professor Chandel, Northwestern University Medical School, Chicago, Illinois. Using fibroblast cultures of patients affected by respiratory chain defects the reasearchers provided genetic evidence that oxygen sensing is dependent on mitochondrial-generated ROS but independent of oxidative phosphorylation.

MARIE CURIE EXCELLENT GRANTS

Erika Fernandez-Vizarra has obtained a Marie Curie Excellent Grant by the European Commision (FP6) for a project on the characterization of disorders caused by nuclear gene mutations leading to defects in the assembly of mitochondrial respiratory chain. The project will take place at the Center for the Study of Mitochondrial Pediatric Diseases