title: Mitochondrial trifunctional protein defects: clinical implications and therapeutic approaches.
abstract: The mitochondrial trifunctional protein (MTP) is a heterotrimeric protein that consists of four alpha-subunits and four beta-subunits and catalyzes three of the four chain-shortening reactions in the mitochondrial beta-oxidation of long-chain fatty acids. Families with recessively inherited MTP defects display a spectrum of maternal and fetal phenotypes. Current management of patients with MTP defects include long-term dietary therapy of fasting avoidance, low-fat/high-carbohydrate diet with restriction of long-chain fatty acid intake and substitution with medium-chain fatty acids. These dietary approaches appear promising in the short-term, but the long-term outcome of patients treated with dietary intervention is largely unknown. Potential therapeutic approaches targeted at correcting the metabolic defect will be discussed. We will discuss the potential use of protein transduction domains that cross the mitochondrial membranes for the treatment of mitochondrial disorders. In addition, we discuss the phenotypes of MTP in a heterozygous state and potential ways to intervene to increase hepatic fatty acid oxidative capacity.
authors.affiliation: Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri 65212, USA.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Rector
authors.forename: R Mark
authors.initials: RM
authors.lastname: Payne
authors.forename: Jamal A
authors.initials: JA
authors.lastname: Ibdah
mesh_terms: D004032:Diet; D005227:Fatty Acids / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D063991:Mitochondrial Trifunctional Protein; D009097:Multienzyme Complexes / Q000235:genetics*; D010084:Oxidation-Reduction; D010641:Phenotype
chemical_list: D005227:Fatty Acids; D009097:Multienzyme Complexes; D063991:Mitochondrial Trifunctional Protein