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Release of mitochondrial Ca 2+ via the permeability transition activates endoplasmic reticulum Ca 2+ uptake
Author(s) -
Bowser David N.,
Petrou Steven,
Panchal Rekha G.,
Smart Megan L.,
Williams David A.
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0828fje
Subject(s) - endoplasmic reticulum , mitochondrial permeability transition pore , cyclopiazonic acid , microbiology and biotechnology , mitochondrion , intracellular , programmed cell death , chemistry , apoptosis , biology , biochemistry
Regulatory interactions between the endoplasmic reticulum (ER) and the mitochondria in the control of intracellular free Ca 2+ concentration ([Ca 2+ ]I), may be of importance in the control of many cell functions, and particularly those involved in initiating cell death. We used targeted Ca 2+ sensors (cameleons) to investigate the movement of Ca 2+ between the ER and mitochondria of intact cells and focused on the role of the mitochondrial permeability transition (MPT) in this interaction. We hypothesized that release of Ca 2+ from mitochondria in response to a known MPT agonist (atractyloside) would cause release of ER Ca 2+ , perpetuating cellular Ca 2+ overload, and cell death. Targeted cameleons (mitochondria and ER) were imaged with confocal microscopy 2–3 days following transient transfection of human embryonic kidney 293 cells. Opening of the MPT resulted in specific loss of mitochondrial Ca 2+ (blocked by cyclosporin A), which was sequestered initially by ER. The ER subsequently released this Ca 2+ load, leading to a global Ca 2+ elevation, a response that was not observed when ER Ca 2+ ‐ATPases were blocked with cyclopiazonic acid. Thus, ER plays an important role in moderating changes in intracellular Ca 2+ following MPT and may play a key role in cell death initiated by mitochondrial mechanisms.