Universität zu Köln

Hlynialuk, Christopher J., Ling, Binbing, Baker, Zakery N., Cobine, Paul A., Yu, Lisa D., Boulet, Aren, Wai, Timothy ORCID: 0000-0002-6770-6222, Hossain, Amzad, El Zawily, Amr M., McFie, Pamela J., Stone, Scot J., Diaz, Francisca, Moraes, Carlos T., Viswanathan, Deepa, Petris, Michael J. and Leary, Scot C. (2015). The Mitochondrial Metallochaperone SCO1 Is Required to Sustain Expression of the High-Affinity Copper Transporter CTR1 and Preserve Copper Homeostasis. Cell Reports, 10 (6). S. 933 - 944. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

Human SCO1 fulfills essential roles in cytochrome c oxidase (COX) assembly and the regulation of copper (Cu) homeostasis, yet it remains unclear why pathogenic mutations in this gene cause such clinically heterogeneous forms of disease. Here, we establish a Sco1 mouse model of human disease and show that ablation of Sco1 expression in the liver is lethal owing to severe COX and Cu deficiencies. We further demonstrate that the Cu deficiency is explained by a functional connection between SCO1 and CTR1, the high-affinity transporter that imports Cu into the cell. CTR1 is rapidly degraded in the absence of SCO1 protein, and we show that its levels are restored in Sco1(-/-) mouse embryonic fibroblasts upon inhibition of the proteasome. These data suggest that mitochondrial signaling through SCO1 provides a post-translational mechanism to regulate CTR1-dependent Cu import into the cell, and they further underpin the importance of mitochondria in cellular Cu homeostasis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hlynialuk, Christopher J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ling, Binbing UNSPECIFIED UNSPECIFIED UNSPECIFIED Baker, Zakery N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cobine, Paul A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Yu, Lisa D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boulet, Aren UNSPECIFIED UNSPECIFIED UNSPECIFIED Wai, Timothy UNSPECIFIED orcid.org/0000-0002-6770-6222 UNSPECIFIED Hossain, Amzad UNSPECIFIED UNSPECIFIED UNSPECIFIED El Zawily, Amr M. UNSPECIFIED UNSPECIFIED UNSPECIFIED McFie, Pamela J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stone, Scot J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Diaz, Francisca UNSPECIFIED UNSPECIFIED UNSPECIFIED Moraes, Carlos T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Viswanathan, Deepa UNSPECIFIED UNSPECIFIED UNSPECIFIED Petris, Michael J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Leary, Scot C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-407440
DOI:	10.1016/j.celrep.2015.01.019
Journal or Publication Title:	Cell Reports
Volume:	10
Number:	6
Page Range:	S. 933 - 944
Date:	2015
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2211-1247
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language C-OXIDASE DEFICIENCY; CANDIDATE GENE; STIMULATED ENDOCYTOSIS; COX DEFICIENCY; MENKES DISEASE; MOUSE MODEL; MUTATIONS; METABOLISM; MECHANISMS; PROTEIN Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40744