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Switching of the homooligomeric ATP‐binding cassette transport complex MDL1 from post‐translational mitochondrial import to endoplasmic reticulum insertion
Author(s) -
Gompf Simone,
Zutz Ariane,
Hofacker Matthias,
Haase Winfried,
van der Does Chris,
Tampé Robert
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.06052.x
Subject(s) - endoplasmic reticulum , atp binding cassette transporter , atp hydrolysis , biochemistry , microbiology and biotechnology , cyclic nucleotide binding domain , biology , mitochondrion , inner mitochondrial membrane , mitochondrial carrier , transporter , nucleotide , bacterial outer membrane , atpase , enzyme , gene , escherichia coli
The ATP‐binding cassette transporter MDL1 of Saccharomyces cerevisiae has been implicated in mitochondrial quality control, exporting degradation products of misassembled respiratory chain complexes. In the present study, we identified an unusually long leader sequence of 59 amino acids, which targets MDL1 to the inner mitochondrial membrane with its nucleotide‐binding domain oriented to the matrix. By contrast, MDL1 lacking this leader sequence is directed into the endoplasmic reticulum membrane with the nucleotide‐binding domain facing the cytosol. Remarkably, in both targeting routes, the ATP‐binding cassette transporter maintains its intrinsic properties of membrane insertion and assembly, leading to homooligomeric complexes with similar activities in ATP hydrolysis. The physiological consequences of both targeting routes were elucidated in cells lacking the mitochondrial ATP‐binding cassette transporter ATM1, which is essential for biogenesis of cytosolic iron‐sulfur proteins. The mitochondrial MDL1 complex can complement ATM1 function, whereas the endoplasmic reticulum‐targeted version, as well as MDL1 mutants deficient in ATP binding and hydrolysis, cannot overcome the Δ atm1 growth phenotype.