Localization of phosphorylated αB-crystallin to heart mitochondria during ischemia-reperfusion

J. K. Jin, R. Whittaker, M. S. Glassy, S. B. Barlow, R. A. Gottlieb, C. C. Glembotski

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

The cytosolic small heat shock protein αB-crystallin (αBC) is a molecular chaperone expressed in large quantities in the heart, where it protects from stresses such as ischemia-reperfusion (I/R). Upon I/R, p38 MAP kinase activation leads to phosphorylation of αBC on Ser59 (P-αBC-S59), which increases its protective ability. αBC confers protection, in part, by interacting with and affecting the functions of key components in stressed cells. We investigated the hypothesis that protection from I/R damage in the heart by P-αBC-S59 can be mediated by localization to mitochondria. We found that P-αBC-S59 localized to mitochondria isolated from untreated mouse hearts and that this localization increased more than threefold when the hearts were subjected to ex vivo I/R. Mitochondrial P-αBC-S59 decreased when hearts were treated with the p38 inhibitor SB-202190. Moreover, SB-202190-treated hearts exhibited more tissue damage and less functional recovery upon reperfusion than controls. I/R activates mitochondrial permeability transition (MPT) pore opening, which increases cell damage. We found that mitochondria incubated with a recombinant mutant form of αBC that mimics P-αBC-S59 exhibited decreased calcium-induced MPT pore opening. These results indicate that mitochondria may be among the key components in stressed cells with which P-αBC-S59 interacts and that this localization may protect the myocardium, in part, by modulating MPT pore opening and, thus, reducing I/R injury.

Original languageEnglish (US)
Pages (from-to)H337-H344
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume294
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

Keywords

  • Cardioprotection
  • Mitochondrial permeability transition

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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