Mitochondrial cardiolipin involved in outer-membrane protein biogenesis: implications for Barth syndrome.
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.
Gebert
Natalia
N
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
Joshi
Amit S
AS
Kutik
Stephan
S
Becker
Thomas
T
McKenzie
Matthew
M
Guan
Xue Li
XL
Mooga
Ved P
VP
Stroud
David A
DA
Kulkarni
Gnanada
G
Wenk
Markus R
MR
Rehling
Peter
P
Meisinger
Chris
C
Ryan
Michael T
MT
Wiedemann
Nils
N
Greenberg
Miriam L
ML
Pfanner
Nikolaus
N
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
D002308:Cardiolipins; D026901:Membrane Transport Proteins