Ca²(+) transfer from the ER to mitochondria: channeling cell death by a tumor suppressor.

Dev Cell 2010 Dec;19(6):789-90

Department of Cell and Developmental Biology, Consortium for Mitochondrial Research, University College London, UK.

The mitochondrial gateway to cell death is a frequent target for tumor suppressors, which largely utilize Bcl-2-dependent apoptotic pathways. Reporting in Science, Giorgi et al. (2010) now show that PML exerts its tumor suppressor function via a distinct mechanism: Ca²(+) transfer from the endoplasmic reticulum to the mitochondria.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.devcel.2010.11.013DOI Listing
December 2010

Publication Analysis

Top Keywords

cell death
8
tumor suppressor
8
ca²+ transfer
8
science giorgi
4
giorgi 2010
4
reporting science
4
apoptotic pathways
4
tumor suppressors
4
suppressors utilize
4
bcl-2-dependent apoptotic
4
2010 pml
4
pathways reporting
4
exerts tumor
4
transfer endoplasmic
4
endoplasmic reticulum
4
reticulum mitochondria
4
mechanism ca²+
4
distinct mechanism
4
target tumor
4
suppressor function
4

Similar Publications

The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family.

Oncogene 2008 Oct;27(50):6419-33

Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec, Canada.

Apoptosis is essential for normal development and maintenance of homeostasis, and disruption of apoptotic pathways is associated with multiple disease states, including cancer. Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 proteins at the endoplasmic reticulum is now well established. Signaling pathways emanating from the endoplasmic reticulum (ER) are involved in apoptosis initiated by stimuli as diverse as ER stress, oncogene expression, death receptor (DR) ligation and oxidative stress, and the BCL-2 family is almost invariably implicated in the regulation of these pathways. Read More

View Article and Full-Text PDF
October 2008

Roles of IP3R and RyR Ca2+ channels in endoplasmic reticulum stress and beta-cell death.

Diabetes 2009 Feb 25;58(2):422-32. Epub 2008 Nov 25.

Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Comlumbia, Canada.

Objective: Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of diabetes, but the roles of specific ER Ca(2+) release channels in the ER stress-associated apoptosis pathway remain unknown. Here, we examined the effects of stimulating or inhibiting the ER-resident inositol trisphosphate receptors (IP(3)Rs) and the ryanodine receptors (RyRs) on the induction of beta-cell ER stress and apoptosis.

Research Design And Methods: Kinetics of beta-cell death were tracked by imaging propidium iodide incorporation and caspase-3 activity in real time. Read More

View Article and Full-Text PDF
February 2009

Inhibition of Ca2+ influx is required for mitochondrial reactive oxygen species-induced endoplasmic reticulum Ca2+ depletion and cell death in leukemia cells.

Mol Pharmacol 2006 Oct 18;70(4):1424-34. Epub 2006 Jul 18.

Arthritis and Immune Disorder Research Centre, University Health Network and Department of Immunology, University of Toronto, Medical Discovery Tower, 8th Floor, Rm 8-356, 101 College St., Toronto, ON, Canada M5G 1L7.

Disturbances of endoplasmic reticulum (ER) Ca2+ homeostasis or protein processing can lead to ER stress-induced cell death. Increasing evidence suggests that oxidative stress (OS) plays an important role in a variety of cell death mechanisms. To investigate the role of OS in ER stress, we measured OS in response to three ER stress agents: econazole (Ec), which stimulates ER Ca2+ release and blocks Ca2+ influx; thapsigargin (Tg), a sarco(endo)plasmic reticulum Ca2+ ATPase inhibitor that releases ER Ca2+ and stimulates Ca2+ influx; and tunicamycin (Tu), a glycosylation inhibitor that causes protein accumulation in the ER. Read More

View Article and Full-Text PDF
October 2006

TRAIL death receptors, Bcl-2 protein family, and endoplasmic reticulum calcium pool.

Vitam Horm 2004 ;67:169-88

Department of Pharmacology State University of New York Upstate Medical University Syracuse, New York 13210, USA.

Calcium (Ca(2+)) is one of the highly versatile second messengers critical in cellular pathophysiology. Alterations in Ca(2+) homeostasis affect many cellular processes, including apoptosis. Recent studies have started to unravel the molecular mechanisms of apoptosis regulation in context to intracellular Ca(2+) pools. Read More

View Article and Full-Text PDF
July 2004