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Conserved roles of Sam50 and metaxins in VDAC biogenesis
Author(s) -
KozjakPavlovic Vera,
Ross Katharina,
Benlasfer Nouhad,
Kimmig Sonja,
Karlas Alexander,
Rudel Thomas
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400982
Subject(s) - voltage dependent anion channel , mitochondrion , biogenesis , microbiology and biotechnology , protein targeting , translocase , translocase of the outer membrane , biology , bacterial outer membrane , cytosol , biochemistry , inner mitochondrial membrane , membrane protein , mitochondrial membrane transport protein , gene , membrane , enzyme , chromosomal translocation , escherichia coli
Voltage‐dependent anion‐selective channel (VDAC) is a β‐barrel protein in the outer mitochondrial membrane that is necessary for metabolite exchange with the cytosol and is proposed to be involved in certain forms of apoptosis. We studied the biogenesis of VDAC in human mitochondria by depleting the components of the mitochondrial import machinery by using RNA interference. Here, we show the importance of the translocase of the outer mitochondrial membrane (TOM) complex in the import of the VDAC precursor. The deletion of Sam50, the central component of the sorting and assembly machinery (SAM), led to both a strong defect in the assembly of VDAC and a reduction in the steady‐state level of VDAC. Metaxin 2‐depleted mitochondria had reduced levels of metaxin 1 and were deficient in import and assembly of VDAC and Tom40, but not of three matrix‐targeted precursors. We also observed a reduction in the levels of metaxin 1 and metaxin 2 in Sam50‐depleted mitochondria, implying a connection between these three proteins, although Sam50 and metaxins seemed to be in different complexes. We conclude that the pathway of VDAC biogenesis in human mitochondria involves the TOM complex, Sam50 and metaxins, and that it is evolutionarily conserved.