Premium
tcBid promotes Ca 2+ signal propagation to the mitochondria: control of Ca 2+ permeation through the outer mitochondrial membrane
Author(s) -
Csordás György,
Madesh Muniswamy,
Antonsson Bruno,
Hajnóczky György
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.9.2198
Subject(s) - mitochondrion , endoplasmic reticulum , biology , microbiology and biotechnology , mitochondrial apoptosis induced channel , calcium signaling , mitochondrial permeability transition pore , mitochondrial membrane transport protein , translocase of the inner membrane , calcium , inner mitochondrial membrane , mitochondrial carrier , bacterial outer membrane , biophysics , signal transduction , apoptosis , programmed cell death , biochemistry , chemistry , organic chemistry , escherichia coli , gene
Calcium spikes established by IP 3 receptor‐mediated Ca 2+ release from the endoplasmic reticulum (ER) are transmitted effectively to the mitochondria, utilizing local Ca 2+ interactions between closely associated subdomains of the ER and mitochondria. Since the outer mitochondrial membrane (OMM) has been thought to be freely permeable to Ca 2+ , investigations have focused on IP 3 ‐driven Ca 2+ transport through the inner mitochondrial membrane (IMM). Here we demonstrate that selective permeabilization of the OMM by tcBid, a proapoptotic protein, results in an increase in the magnitude of the IP 3 ‐induced mitochondrial [Ca 2+ ] signal. This effect of tcBid was due to promotion of activation of Ca 2+ uptake sites in the IMM and, in turn, to facilitation of mitochondrial Ca 2+ uptake. In contrast, tcBid failed to control the delivery of sustained and global Ca 2+ signals to the mitochondria. Thus, our data support a novel model that Ca 2+ permeability of the OMM at the ER– mitochondrial interface is an important determinant of local Ca 2+ signalling. Facilitation of Ca 2+ delivery to the mitochondria by tcBid may also support recruitment of mitochondria to the cell death machinery.