Organ-specific regulation of ATP7A abundance is coordinated with systemic copper homeostasis

Haarin Chun, Tracy Catterton, Heejeong Kim, Jaekwon Lee, Byung Eun Kim

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Copper (Cu) is an essential cofactor for various enzymatic activities including mitochondrial electron transport, iron mobilization, and peptide hormone maturation. Consequently, Cu dysregulation is associated with fatal neonatal disease, liver and cardiac dysfunction, and anemia. While the Cu transporter ATP7A plays a major role in both intestinal Cu mobilization to the periphery and prevention of Cu over-accumulation, it is unclear how regulation of ATP7A contributes to Cu homeostasis in response to systemic Cu fluctuation. Here we show, using Cu-deficient mouse models, that steady-state levels of ATP7A are lower in peripheral tissues (including the heart, spleen, and liver) under Cu deficiency and that subcutaneous administration of Cu to these animals restore normal ATP7A levels in these tissues. Strikingly, ATP7A in the intestine is regulated in the opposite manner - low systemic Cu increases ATP7A while subcutaneous Cu administration decreases ATP7A suggesting that intestine-specific non-autonomous regulation of ATP7A abundance may serve as a key homeostatic control for Cu export into the circulation. Our results support a systemic model for how a single transporter can be inversely regulated in a tissue-specific manner to maintain organismal Cu homeostasis.

Original languageEnglish (US)
Article number12001
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Copper
Homeostasis
Intestines
Infant, Newborn, Diseases
Peptide Hormones
Electron Transport
Liver Diseases
Anemia
Spleen
Iron
Liver

ASJC Scopus subject areas

  • General

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Organ-specific regulation of ATP7A abundance is coordinated with systemic copper homeostasis. / Chun, Haarin; Catterton, Tracy; Kim, Heejeong; Lee, Jaekwon; Kim, Byung Eun.

In: Scientific reports, Vol. 7, No. 1, 12001, 01.12.2017.

Research output: Contribution to journalArticle

Chun, Haarin ; Catterton, Tracy ; Kim, Heejeong ; Lee, Jaekwon ; Kim, Byung Eun. / Organ-specific regulation of ATP7A abundance is coordinated with systemic copper homeostasis. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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