Mitochondrial cardiolipin involved in outer-membrane protein biogenesis: implications for Barth syndrome

Curr Biol. 2009 Dec 29;19(24):2133-9. doi: 10.1016/j.cub.2009.10.074. Epub 2009 Dec 3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoradiography
  • Barth Syndrome / metabolism*
  • Barth Syndrome / physiopathology
  • Cardiolipins / genetics
  • Cardiolipins / metabolism*
  • Cell Line
  • Electrophoresis
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Immunoblotting
  • Membrane Transport Proteins / biosynthesis*
  • Membrane Transport Proteins / metabolism
  • Mitochondria / metabolism*
  • Mitochondrial Membranes / chemistry*
  • Saccharomyces cerevisiae


  • Cardiolipins
  • Membrane Transport Proteins