title: LRP130 protein remodels mitochondria and stimulates fatty acid oxidation.
abstract: Impaired oxidative phosphorylation (OXPHOS) is implicated in several metabolic disorders. Even though mitochondrial DNA encodes several subunits critical for OXPHOS, the metabolic consequence of activating mitochondrial transcription remains unclear. We show here that LRP130, a protein involved in Leigh syndrome, increases hepatic β-fatty acid oxidation. Using convergent genetic and biochemical approaches, we demonstrate LRP130 complexes with the mitochondrial RNA polymerase to activate mitochondrial transcription. Activation of mitochondrial transcription is associated with increased OXPHOS activity, increased supercomplexes, and denser cristae, independent of mitochondrial biogenesis. Consistent with increased oxidative phosphorylation, ATP levels are increased in both cells and mouse liver, whereas coupled respiration is increased in cells. We propose activation of mitochondrial transcription remodels mitochondria and enhances oxidative metabolism.
authors.affiliation: Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Lijun
authors.initials: L
authors.lastname: Liu
authors.affiliation: Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Masato
authors.initials: M
authors.lastname: Sanosaka
authors.affiliation: Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Shi
authors.initials: S
authors.lastname: Lei
authors.affiliation: Departments of Pathology and Genetics, Yale University School of Medicine, New Haven, Connecticut 06520.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Bestwick
authors.affiliation: Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Frey
authors.affiliation: Departments of Pathology and Genetics, Yale University School of Medicine, New Haven, Connecticut 06520.
authors.forename: Yulia V
authors.initials: YV
authors.lastname: Surovtseva
authors.affiliation: Departments of Pathology and Genetics, Yale University School of Medicine, New Haven, Connecticut 06520.
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Shadel
authors.affiliation: Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605. Electronic address: marcus.cooper@umassmed.edu.
authors.forename: Marcus P
authors.initials: MP
authors.lastname: Cooper
mesh_terms: D000818:Animals; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D007888:Leigh Disease / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008930:Mitochondria, Liver / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D005227:Fatty Acids; C087940:LRPPRC protein, human; C486222:Lrpprc protein, mouse; D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D012321:DNA-Directed RNA Polymerases