Overexpressing GRP78 influences Ca2+ handling and function of mitochondria in astrocytes after ischemia-like stress.
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.
Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA.
Yi-Bing
YB
Ouyang
Li-Jun
LJ
Xu
John F
JF
Emery
Amy S
AS
Lee
Rona G
RG
Giffard
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D007511:Ischemia / Q000378:metabolism* / Q000503:physiopathology; D008564:Membrane Potentials; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D017382:Reactive Oxygen Species; D002118:Calcium