Heat shock protein 90β1 is essential for polyunsaturated fatty acid-induced mitochondrial Ca2+ efflux

Hua Zhang, Zhen Hua Li, Michael Q. Zhang, Michael S. Katz, Bin Xian Zhang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Nonesterified fatty acids may influence mitochondrial function by alterations in gene expression, metabolism, and/or mitochondrial Ca2+ ([Ca2+]m) homeostasis. We have previously reported that polyunsaturated fatty acids induce Ca2+ efflux from mitochondria, an action that may deplete [Ca2+]m and thus contribute to nonesterified fatty acid-responsive mitochondrial dysfunction. Here we show that the chaperone protein heat shock protein 90 β1 (hsp90β1) is required for polyunsaturated fatty acid-induced mitochondrial Ca2+ efflux (PIMCE). Retinoic acid induced differentiation of human teratocarcinoma NT2 cells in association with attenuation of PIMCE. Proteomic analysis of mitochondrial proteins revealed that hsp90β1, among other proteins, was reduced in retinoic acid-differentiated cells. Blockade of PIMCE in NT2 cells by 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin, a known inhibitor of the chaperone activity of hsp90, and hsp90β1 RNA interference demonstrated that hsp90β1 is essential for PIMCE. We also show localization of hsp90β1 in mitochondria by Western blot and immunofluorescence. Distinctive effects of inhibitors binding to the N or C terminus of hsp90 on PIMCE in isolated mitochondria suggested that the C terminus of hsp90β1 plays a critical role in PIMCE.

Original languageEnglish (US)
Pages (from-to)7580-7589
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number12
DOIs
StatePublished - Mar 21 2008

Fingerprint

Essential Fatty Acids
HSP90 Heat-Shock Proteins
Heat-Shock Proteins
Unsaturated Fatty Acids
Mitochondria
17-(dimethylaminoethylamino)-17-demethoxygeldanamycin
Tretinoin
Nonesterified Fatty Acids
Teratocarcinoma
Mitochondrial Proteins
RNA Interference
Metabolism
Gene expression
Proteomics
Fluorescent Antibody Technique
Proteins
Homeostasis
Western Blotting
RNA
Gene Expression

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Heat shock protein 90β1 is essential for polyunsaturated fatty acid-induced mitochondrial Ca2+ efflux. / Zhang, Hua; Li, Zhen Hua; Zhang, Michael Q.; Katz, Michael S.; Zhang, Bin Xian.

In: Journal of Biological Chemistry, Vol. 283, No. 12, 21.03.2008, p. 7580-7589.

Research output: Contribution to journalArticle

Zhang, Hua ; Li, Zhen Hua ; Zhang, Michael Q. ; Katz, Michael S. ; Zhang, Bin Xian. / Heat shock protein 90β1 is essential for polyunsaturated fatty acid-induced mitochondrial Ca2+ efflux. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 12. pp. 7580-7589.
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