title: Mitochondrial cardiolipin involved in outer-membrane protein biogenesis: implications for Barth syndrome.
abstract: The biogenesis of mitochondria requires the import of a large number of proteins from the cytosol [1, 2]. Although numerous studies have defined the proteinaceous machineries that mediate mitochondrial protein sorting, little is known about the role of lipids in mitochondrial protein import. Cardiolipin, the signature phospholipid of the mitochondrial inner membrane [3-5], affects the stability of many inner-membrane protein complexes [6-12]. Perturbation of cardiolipin metabolism leads to the X-linked cardioskeletal myopathy Barth syndrome [13-18]. We report that cardiolipin affects the preprotein translocases of the mitochondrial outer membrane. Cardiolipin mutants genetically interact with mutants of outer-membrane translocases. Mitochondria from cardiolipin yeast mutants, as well as Barth syndrome patients, are impaired in the biogenesis of outer-membrane proteins. Our findings reveal a new role for cardiolipin in protein sorting at the mitochondrial outer membrane and bear implications for the pathogenesis of Barth syndrome.
authors: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors: Natalia
authors: N
authors: Gebert
authors: Amit S
authors: AS
authors: Joshi
authors: Stephan
authors: S
authors: Kutik
authors: Thomas
authors: T
authors: Becker
authors: Matthew
authors: M
authors: McKenzie
authors: Xue Li
authors: XL
authors: Guan
authors: Ved P
authors: VP
authors: Mooga
authors: David A
authors: DA
authors: Stroud
authors: Gnanada
authors: G
authors: Kulkarni
authors: Markus R
authors: MR
authors: Wenk
authors: Peter
authors: P
authors: Rehling
authors: Chris
authors: C
authors: Meisinger
authors: Michael T
authors: MT
authors: Ryan
authors: Nils
authors: N
authors: Wiedemann
authors: Miriam L
authors: ML
authors: Greenberg
authors: Nikolaus
authors: N
authors: Pfanner
mesh_terms: D001345:Autoradiography; D056889:Barth Syndrome / Q000378:metabolism* / Q000503:physiopathology; D002308:Cardiolipins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004586:Electrophoresis; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015151:Immunoblotting; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000737:chemistry*; D012441:Saccharomyces cerevisiae
chemical_list: D002308:Cardiolipins; D026901:Membrane Transport Proteins