Klein, Julian M. and Schwarz, Guenter ORCID: 0000-0002-2118-9338 (2012). Cofactor-dependent maturation of mammalian sulfite oxidase links two mitochondrial import pathways. J. Cell Sci., 125 (20). S. 4876 - 4886. CAMBRIDGE: COMPANY BIOLOGISTS LTD. ISSN 1477-9137

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Abstract

Sulfite oxidase (SO) catalyses the metabolic detoxification of sulfite to sulfate within the intermembrane space of mitochondria. The enzyme follows a complex maturation pathway, including mitochondrial transport and processing, integration of two prosthetic groups, molybdenum cofactor (Moco) and heme, as well as homodimerisation. We have identified the sequential and cofactor-dependent maturation steps of SO. The N-terminal bipartite targeting signal of SO was required but not sufficient for mitochondrial localization. In the absence of Moco, most of the SO, although processed by the inner membrane peptidase of mitochondria, was found in the cytosol. Moco binding was required to induce mitochondrial trapping and retention, thus ensuring unidirectional translocation of SO. In the absence of the N-terminal targeting sequence, SO assembled in the cytosol, suggesting an important function for the leader sequence in preventing premature cofactor binding. In vivo, heme binding and dimerisation did not occur in the absence of Moco and only occurred after Moco integration. In conclusion, the identified molecular hierarchy of SO maturation represents a novel link between the canonical presequence pathway and folding-trap mechanisms of mitochondrial import.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Klein, Julian M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwarz, GuenterUNSPECIFIEDorcid.org/0000-0002-2118-9338UNSPECIFIED
URN: urn:nbn:de:hbz:38-481025
DOI: 10.1242/jcs.110114
Journal or Publication Title: J. Cell Sci.
Volume: 125
Number: 20
Page Range: S. 4876 - 4886
Date: 2012
Publisher: COMPANY BIOLOGISTS LTD
Place of Publication: CAMBRIDGE
ISSN: 1477-9137
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MOLYBDENUM COFACTOR; INTERMEMBRANE SPACE; YEAST MITOCHONDRIA; OUTER-MEMBRANE; NITRATE REDUCTASE; CYTOCHROME-C; BIOSYNTHESIS; PROTEINS; DEFICIENCY; HEMEMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48102

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