Universität zu Köln

Klein, Julian M., Busch, Jakob D., Potting, Christoph, Baker, Michael J., Langer, Thomas ORCID: 0000-0003-1250-1462 and Schwarz, Guenter ORCID: 0000-0002-2118-9338 (2012). The Mitochondrial Amidoxime-reducing Component (mARC1) Is a Novel Signal-anchored Protein of the Outer Mitochondrial Membrane. J. Biol. Chem., 287 (51). S. 42795 - 42804. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

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Abstract

The mitochondrial amidoxime-reducing component (mARC) was recently discovered as the fifth eukaryotic molybdenum cofactor-containing enzyme. The human genome encodes two mARC proteins, mARC1 and mARC2, sharing significant homologies with respect to sequence and function. Whereas mARC2 was identified as a mitochondrial enzyme, the subcellular localization of mARC1 has remained uncharacterized, although the similarity of both proteins suggested identical subcellular localizations. In addition, neither mARC1 nor mARC2 could be attributed unambiguously to one of the four mitochondrial subcompartments. Accordingly, mechanisms triggering the subcellular distribution of both enzymes have been unexplored so far. Here, we shed light on the subcellular localization of mARC1 and demonstrate that it is integrated into the outer mitochondrial membrane. The C-terminal catalytic domain of the protein remains exposed to the cytosol and confers an N-(in)-C-(out) membrane orientation of mARC1. This localization is triggered by the N terminus of the enzyme, being composed of a weak N-terminal mitochondrial targeting signal and a downstream transmembrane helix. We demonstrate the transmembrane domain of mARC1 to be sufficient for mitochondrial targeting and the N-terminal targeting signal to function as a supportive receptor for the outer mitochondrial membrane. According to its localization and targeting mechanism, we classify mARC1 as a novel signal-anchored mitochondrial protein. During mitochondrial import, mARC1 is not processed, and membrane integration proceeds membrane potential independently but requires external ATP, which finally results in the assembly of mARC1 into high oligomeric protein complexes.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Klein, Julian M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Busch, Jakob D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Potting, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Baker, Michael J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Langer, Thomas UNSPECIFIED orcid.org/0000-0003-1250-1462 UNSPECIFIED Schwarz, Guenter UNSPECIFIED orcid.org/0000-0002-2118-9338 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-476686
DOI:	10.1074/jbc.M112.419424
Journal or Publication Title:	J. Biol. Chem.
Volume:	287
Number:	51
Page Range:	S. 42795 - 42804
Date:	2012
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	BETHESDA
ISSN:	1083-351X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CYTOCHROME-B5-LIKE HEMOPROTEIN; LIVER-MITOCHONDRIA; REDUCTASE; TRANSLOCATION; IMPORT; SYSTEM Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47668