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Endoplasmic reticulum BIK initiates DRP1‐regulated remodelling of mitochondrial cristae during apoptosis
Author(s) -
Germain Marc,
Mathai Jaigi P,
McBride Heidi M,
Shore Gordon C
Publication year - 2005
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 - 10.1038/sj.emboj.7600592
Subject(s) - endoplasmic reticulum , biology , mitochondrion , microbiology and biotechnology , mitochondrial apoptosis induced channel , mitochondrial fission , cytosol , cytochrome c , apoptosome , organelle , caspase , apoptosis , programmed cell death , biochemistry , enzyme
The endoplasmic reticulum (ER) can elicit proapoptotic signalling that results in transmission of Ca 2+ to the mitochondria, which in turn stimulates recruitment of the fission enzyme DRP1 to the surface of the organelle. Here, we show that BH3‐only BIK activates this pathway at the ER in intact cells, resulting in mitochondrial fragmentation but little release of cytochrome c to the cytosol. The BIK‐induced transformations in mitochondria are dynamic in nature and involve DRP1‐dependent remodelling and opening of cristae, where the major stores of cytochrome c reside. This novel function for DRP1 is distinct from its recognized role in regulating mitochondrial fission. Selective permeabilization of the outer membrane with digitonin confirmed that BIK stimulation results in mobilization of intramitochondrial cytochrome c . Of note, BIK can cooperate with a weak BH3‐only protein that targets mitochondria, such as NOXA, to activate BAX by a mechanism that is independent of DRP1 enzyme activity. When expressed together, BIK and NOXA cause rapid release of mobilized cytochrome c and activation of caspases.