Murschall, Lena Maria, Gerhards, Anne, MacVicar, Thomas, Peker, Esra, Hasberg, Lidwina, Wawra, Stephan, Langer, Thomas and Riemer, Jan (2020). The C-terminal region of the oxidoreductase MIA40 stabilizes its cytosolic precursor during mitochondrial import. BMC Biol., 18 (1). LONDON: BMC. ISSN 1741-7007
Full text not available from this repository.Abstract
Background The mitochondrial intermembrane space (IMS) is home to proteins fulfilling numerous essential cellular processes, particularly in metabolism and mitochondrial function. All IMS proteins are nuclear encoded and synthesized in the cytosol and must therefore be correctly targeted and transported to the IMS, either through mitochondrial targeting sequences or conserved cysteines and the mitochondrial disulfide relay system. The mitochondrial oxidoreductase MIA40, which catalyzes disulfide formation in the IMS, is imported by the combined action of the protein AIFM1 and MIA40 itself. Here, we characterized the function of the conserved highly negatively charged C-terminal region of human MIA40. Results We demonstrate that the C-terminal region is critical during posttranslational mitochondrial import of MIA40, but is dispensable for MIA40 redox function in vitro and in intact cells. The C-terminal negatively charged region of MIA40 slowed import into mitochondria, which occurred with a half-time as slow as 90 min. During this time, the MIA40 precursor persisted in the cytosol in an unfolded state, and the C-terminal negatively charged region served in protecting MIA40 from proteasomal degradation. This stabilizing property of the MIA40 C-terminal region could also be conferred to a different mitochondrial precursor protein, COX19. Conclusions Our data suggest that the MIA40 precursor contains the stabilizing information to allow for postranslational import of sufficient amounts of MIA40 for full functionality of the essential disulfide relay. We thereby provide for the first time mechanistic insights into the determinants controlling cytosolic surveillance of IMS precursor proteins.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||
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| URN: | urn:nbn:de:hbz:38-323777 | ||||||||||||||||||||||||||||||||||||
| DOI: | 10.1186/s12915-020-00824-1 | ||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | BMC Biol. | ||||||||||||||||||||||||||||||||||||
| Volume: | 18 | ||||||||||||||||||||||||||||||||||||
| Number: | 1 | ||||||||||||||||||||||||||||||||||||
| Date: | 2020 | ||||||||||||||||||||||||||||||||||||
| Publisher: | BMC | ||||||||||||||||||||||||||||||||||||
| Place of Publication: | LONDON | ||||||||||||||||||||||||||||||||||||
| ISSN: | 1741-7007 | ||||||||||||||||||||||||||||||||||||
| Language: | English | ||||||||||||||||||||||||||||||||||||
| Faculty: | Faculty of Mathematics and Natural Sciences | ||||||||||||||||||||||||||||||||||||
| Divisions: | Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry | ||||||||||||||||||||||||||||||||||||
| Subjects: | no entry | ||||||||||||||||||||||||||||||||||||
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| Refereed: | Yes | ||||||||||||||||||||||||||||||||||||
| URI: | http://kups.ub.uni-koeln.de/id/eprint/32377 |
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