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Mitochondrion. 2011 Mar;11(2):279-86. doi: 10.1016/j.mito.2010.10.007. Epub 2010 Nov 1.

Overexpressing GRP78 influences Ca2+ handling and function of mitochondria in astrocytes after ischemia-like stress.

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1
Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA.

Abstract

Ca(2+) transfer from endoplasmic reticulum (ER) to mitochondria at contact sites between the organelles can induce mitochondrial dysfunction and programmed cell death after stress. The ER-localized chaperone glucose-regulated protein 78kDa (GRP78/BiP) protects neurons against excitotoxicity and apoptosis. Here we show that overexpressing GRP78 protects astrocytes against ischemic injury, reduces net flux of Ca(2+) from ER to mitochondria, increases Ca(2+) uptake capacity in isolated mitochondria, reduces free radical production, and preserves respiratory activity and mitochondrial membrane potential after stress. We conclude that GRP78 influences ER-mitochondrial Ca(2+) crosstalk to maintain mitochondrial function and protect astrocytes from ischemic injury.

PMID:
21047562
PMCID:
PMC3037025
DOI:
10.1016/j.mito.2010.10.007
[Indexed for MEDLINE]
Free PMC Article
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