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Inhibiting the mitochondrial fission machinery does not prevent Bax/Bak-dependent apoptosis.


ABSTRACT: Apoptosis, induced by a number of death stimuli, is associated with a fragmentation of the mitochondrial network. These morphological changes in mitochondria have been shown to require proteins, such as Drp1 or hFis1, which are involved in regulating the fission of mitochondria. However, the precise role of mitochondrial fission during apoptosis remains elusive. Here we report that inhibiting the fission machinery in Bax/Bak-mediated apoptosis, by down-regulating of Drp1 or hFis1, prevents the fragmentation of the mitochondrial network and partially inhibits the release of cytochrome c from the mitochondria but fails to block the efflux of Smac/DIABLO. In addition, preventing mitochondrial fragmentation does not inhibit cell death induced by Bax/Bak-dependent death stimuli, in contrast to the effects of Bcl-xL or caspase inhibition. Therefore, the fission of mitochondria is a dispensable event in Bax/Bak-dependent apoptosis.

SUBMITTER: Parone PA 

PROVIDER: S-EPMC1636857 | biostudies-other | 2006 Oct

REPOSITORIES: biostudies-other

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Inhibiting the mitochondrial fission machinery does not prevent Bax/Bak-dependent apoptosis.

Parone Philippe A PA   James Dominic I DI   Da Cruz Sandrine S   Mattenberger Yves Y   Donzé Olivier O   Barja François F   Martinou Jean-Claude JC  

Molecular and cellular biology 20061001 20


Apoptosis, induced by a number of death stimuli, is associated with a fragmentation of the mitochondrial network. These morphological changes in mitochondria have been shown to require proteins, such as Drp1 or hFis1, which are involved in regulating the fission of mitochondria. However, the precise role of mitochondrial fission during apoptosis remains elusive. Here we report that inhibiting the fission machinery in Bax/Bak-mediated apoptosis, by down-regulating of Drp1 or hFis1, prevents the f  ...[more]

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