title: Frataxin activates mitochondrial energy conversion and oxidative phosphorylation.
abstract: Friedreich's ataxia (FA) is an autosomal recessive disease caused by decreased expression of the mitochondrial protein frataxin. The biological function of frataxin is unclear. The homologue of frataxin in yeast, YFH1, is required for cellular respiration and was suggested to regulate mitochondrial iron homeostasis. Patients suffering from FA exhibit decreased ATP production in skeletal muscle. We now demonstrate that overexpression of frataxin in mammalian cells causes a Ca(2+)-induced up-regulation of tricarboxylic acid cycle flux and respiration, which, in turn, leads to an increased mitochondrial membrane potential (delta psi(m)) and results in an elevated cellular ATP content. Thus, frataxin appears to be a key activator of mitochondrial energy conversion and oxidative phosphorylation.
authors.affiliation: Joslin Diabetes Center, Harvard Medical School, Research Division, Boston, MA 02215, USA. michael.ristow@uni-koeln.de
authors.forename: M
authors.initials: M
authors.lastname: Ristow
authors.forename: M F
authors.initials: MF
authors.lastname: Pfister
authors.forename: A J
authors.initials: AJ
authors.lastname: Yee
authors.forename: M
authors.initials: M
authors.lastname: Schubert
authors.forename: L
authors.initials: L
authors.lastname: Michael
authors.forename: C Y
authors.initials: CY
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Ueki
authors.forename: M D
authors.initials: MD
authors.lastname: Michael
authors.forename: B B
authors.initials: BB
authors.lastname: Lowell
authors.forename: C R
authors.initials: CR
authors.lastname: Kahn
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002952:Citric Acid Cycle; D004734:Energy Metabolism; D005621:Friedreich Ataxia / Q000378:metabolism*; D033862:Iron-Binding Proteins; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D010085:Oxidative Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism* / Q000502:physiology; D014280:Triglycerides / Q000096:biosynthesis; D000096923:Frataxin
chemical_list: D002118:Calcium; D033862:Iron-Binding Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D014280:Triglycerides; D000096923:Frataxin