Format

Send to

Choose Destination
Cell Calcium. 2011 Sep;50(3):222-33. doi: 10.1016/j.ceca.2011.04.007. Epub 2011 May 23.

Mitochondrial permeability transition in Ca(2+)-dependent apoptosis and necrosis.

Author information

1
Department of Biomedical Sciences and CNR Institute of Neuroscience, University of Padova, Italy. rasola@bio.unipd.it

Abstract

A variety of stimuli utilize an increase of cytosolic free Ca(2+) concentration as a second messenger to transmit signals, through Ca(2+) release from the endoplasmic reticulum or opening of plasma membrane Ca(2+) channels. Mitochondria contribute to the tight spatiotemporal control of this process by accumulating Ca(2+), thus shaping the return of cytosolic Ca(2+) to resting levels. The rise of mitochondrial matrix free Ca(2+) concentration stimulates oxidative metabolism; yet, in the presence of a variety of sensitizing factors of pathophysiological relevance, the matrix Ca(2+) increase can also lead to opening of the permeability transition pore (PTP), a high conductance inner membrane channel. While transient openings may serve the purpose of providing a fast Ca(2+) release mechanism, persistent PTP opening is followed by deregulated release of matrix Ca(2+), termination of oxidative phosphorylation, matrix swelling with inner membrane unfolding and eventually outer membrane rupture with release of apoptogenic proteins and cell death. Thus, a rise in mitochondrial Ca(2+) can convey both apoptotic and necrotic death signals by inducing opening of the PTP. Understanding the signalling networks that govern changes in mitochondrial free Ca(2+) concentration, their interplay with Ca(2+) signalling in other subcellular compartments, and regulation of PTP has important implications in the fine comprehension of the main biological routines of the cell and in disease pathogenesis.

PMID:
21601280
DOI:
10.1016/j.ceca.2011.04.007
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center