Title of article :
A Tag at the Carboxy Terminus Prevents Membrane Integration of VDAC1 in Mammalian Mitochondria
Author/Authors :
Vera Kozjak-Pavlovic، نويسنده , , Katharina Ross، نويسنده , , Monika G?tz، نويسنده , , Christian Goosmann، نويسنده , , Thomas Rudel، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2010
Pages :
14
From page :
219
To page :
232
Abstract :
β-Barrel proteins are found in the outer membranes of bacteria, chloroplasts and mitochondria. The evolutionary conserved sorting and assembly machinery (SAM complex) assembles mitochondrial β-barrel proteins, such as voltage-dependent anion-selective channel 1 (VDAC1), into complexes in the outer membrane by recognizing a sorting β-signal in the carboxy-terminal part of the protein. Here we show that in mammalian mitochondria, masking of the C-terminus of β-barrel proteins by a tag leads to accumulation of soluble misassembled protein in the intermembrane space, which causes mitochondrial fragmentation and loss of membrane potential. A similar phenotype is observed if the β-signal is shortened, removed or when the conserved hydrophobic residues in the β-signal are mutated. The length of the tag at the C-terminus is critical for the assembly of VDAC1, as well as the amino acid residues at positions 130, 222, 225 and 251 of the protein. We propose that if the recognition of the β-signal or the folding of the β-barrel proteins is inhibited, the nonassembled protein will accumulate in the intermembrane space, aggregate and damage mitochondria. This effect offers easy tools for studying the requirements for the membrane assembly of β-barrel proteins, but also advises caution when interpreting the outcome of the β-barrel protein overexpression experiments.
Keywords :
?-barrel , SAM , VDAC , Mitochondria , protein import
Journal title :
Journal of Molecular Biology
Serial Year :
2010
Journal title :
Journal of Molecular Biology
Record number :
1251357
Link To Document :
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