title: Alterations in the heart mitochondrial proteome in a desmin null heart failure model.
abstract: Desmin, the major muscle-specific intermediate filament (IF) protein, is essential for mitochondrial behavior and function and maintenance of healthy muscle. Mice null for desmin develop dilated cardiomyopathy characterized by extensive cardiomyocyte death, fibrosis, calcification and eventual heart failure. We sought to investigate the heart mitochondrial proteome of wild type and desmin null mice in order to understand the cardiac and skeletal myopathy phenotype of desmin deficiency. The proteins were analyzed by 2-D electrophoresis, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Three hundred and eighty different gene products were identified, about 50% of which were enzyme subunits. Cytoskeletal and muscle-specific proteins, calcium-binding proteins, proteins with various other functions and about 70 unknown, hypothetical or poorly described gene products, were also identified. We have observed differences in most metabolic pathways, in apoptosis, calcium homeostasis, calcification and fibrosis and in different signaling pathways linked or not to mitochondrial function. The most significant changes were observed in ketone body and acetate metabolism, NADH shuttle proteins, amino-acid metabolism proteins and respiratory enzymes. Several of these changes are consistent with the known phenotype of desmin deficiency.
authors.affiliation: Center of Basic Research, Foundation for Biomedical Research, Academy of Athens, Soranou Efessiou 4, 11527 Athens, Greece; F. Hoffmann-La Roche Ltd., Center for Medical Genomics, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Fountoulakis
authors.forename: Elisavet
authors.initials: E
authors.lastname: Soumaka
authors.forename: Kleopatra
authors.initials: K
authors.lastname: Rapti
authors.forename: Manolis
authors.initials: M
authors.lastname: Mavroidis
authors.forename: George
authors.initials: G
authors.lastname: Tsangaris
authors.forename: Antony
authors.initials: A
authors.lastname: Maris
authors.forename: Noah
authors.initials: N
authors.lastname: Weisleder
authors.forename: Yassemi
authors.initials: Y
authors.lastname: Capetanaki
mesh_terms: D019342:Acetic Acid / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism*; D030562:Databases, Protein; D003893:Desmin / Q000172:deficiency* / Q000235:genetics; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D066298:In Vitro Techniques; D007657:Ketone Bodies / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000302:isolation & purification / Q000378:metabolism; D010084:Oxidation-Reduction; D018272:Porins / Q000378:metabolism; D020543:Proteome / Q000302:isolation & purification / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D050994:Voltage-Dependent Anion Channels
chemical_list: D000596:Amino Acids; D003893:Desmin; D007657:Ketone Bodies; D008293:Malates; D024101:Mitochondrial Proteins; D018272:Porins; D020543:Proteome; D050994:Voltage-Dependent Anion Channels; D001224:Aspartic Acid; C030298:malic acid; D019342:Acetic Acid