tailieunhanh - Báo cáo khoa học: Frataxin deficiency causes upregulation of mitochondrial Lon and ClpP proteases and severe loss of mitochondrial Fe–S proteins

Friedreich ataxia (FRDA) is a rare hereditary neurodegenerative disease characterized by progressive ataxia and cardiomyopathy. The cause of the disease is a defect in mitochondrial frataxin, an iron chaperone involved in the maturation of Fe–S cluster proteins. | Frataxin deficiency causes upregulation of mitochondrial Lon and ClpP proteases and severe loss of mitochondrial Fe-S proteins Blanche Guillon1 Anne-Laure Bulteau2 Marie Wattenhofer-Donze3 4 Stephane Schmucker3 5 Bertrand Friguet2 Helene Puccio3 4 5 6 7 Jean-Claude Drapier1 and Cecile Bouton1 1 Institut de Chimie des Substances Naturelles Centre Nationalde la Recherche Scientifique Gif-sur-Yvette France 2 Laboratoire de Biologie et Biochimie Cellulaire du Vieillissement Universite Paris 7 France 3 IGBMC Institut de Genetique et de Biologie Moleculaire et Cellulaire Illkirch France 4 College de France Chaire de genetique humaine Illkirch France 5 Universite Louis Pasteur Strasbourg France 6 Inserm U596 Illkirch France 7 CNRS UMR7104 Illkirch France Keywords ClpP frataxin Friedreich ataxia iron-sulfur cluster Lon protease Correspondence C. Bouton ICSN-CNRS Avenue de la Terrasse 91190 Gif-sur-Yvette France Fax 33 1 69 07 72 47 Tel 33 1 69 82 30 10 E-mail Received 21 October 2008 revised 4 December 2008 accepted 9 December 2008 doi Friedreich ataxia FRDA is a rare hereditary neurodegenerative disease characterized by progressive ataxia and cardiomyopathy. The cause of the disease is a defect in mitochondrial frataxin an iron chaperone involved in the maturation of Fe-S cluster proteins. Several human diseases including cardiomyopathies have been found to result from deficiencies in the activity of specific proteases which have important roles in protein turnover and in the removal of damaged or unneeded protein. In this study using the muscle creatine kinase mouse heart model for FRDA we show a clear progressive increase in protein levels of two important mitochondrial ATP-dependent proteases Lon and ClpP in the hearts of muscle creatine kinase mutants. These proteases have been shown to degrade unfolded and damaged proteins in the matrix of mitochondria. Their upregulation which was triggered at a .