Mitochondrial Cardiolipin Involved in Outer-Membrane Protein Biogenesis: Implications for Barth Syndrome

• DOI: 10.1016/j.cub.2009.10.074
• Publication Date: 2009-12-07T10:11:54Z
• Authors: Natalia Gebert; Amit S. Joshi; Stephan Kutik; Thomas Becker; Matthew McKenzie; Xue Li Guan; Ved P. Mooga; David A. Stroud; Gnanada Kulkarni; Markus R. Wenk; Peter Rehling; Chris Meisinger; Michael T. Ryan; Nils Wiedemann; Miriam L. Greenberg; Nikolaus Pfanner
• Keywords: Electrophoresis; 0301 basic medicine; Agricultural and Biological Sciences(all); Biochemistry, Genetics and Molecular Biology(all); Cardiolipins; Immunoblotting; 610; Membrane Transport Proteins; Saccharomyces cerevisiae; Cell Line; Mitochondria; 03 medical and health sciences; 0601 (four-digit-FOR); 616; Barth Syndrome; Mitochondrial Membranes; Autoradiography; Humans; CELLBIO; Electrophoresis, Polyacrylamide Gel; 060108 Protein Trafficking

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.