Role for CED-9 and Egl-1 as regulators of mitochondrial fission and fusion dynamics

Delivani, Petrina, Adrain, Colin, Taylor, Rebecca C., Duriez, Patrick J. and Martin, Seamus J. (2006) Role for CED-9 and Egl-1 as regulators of mitochondrial fission and fusion dynamics. Molecular Cell, 21 (6), 761-773. (doi:10.1016/j.molcel.2006.01.034). (PMID:16543141)

Abstract

Bcl-2 family proteins play central roles in apoptosis by regulating the release of mitochondrial intermembrane space proteins such as cytochrome c. Death-promoting Bcl-2 family members, such as Bax, can promote cytochrome c release and fragmentation of the mitochondrial network, whereas apoptosis-inhibitory members, such as Bcl-2 and Bcl-xL, can antagonize these events. It remains unclear whether CED-9, the worm Bcl-2 relative, can regulate mitochondrial fission/fusion dynamics or the release of proteins from the mitochondrial intermembrane space. Here, we show that CED-9 interacts with Mitofusin-2/fuzzy onions and can promote mitochondrial clustering and dramatic reorganization of mitochondrial networks. Consistent with its ability to neutralize CED-9 function, EGL-1 antagonized CED-9-dependent remodeling of the mitochondrial network. However, CED-9 failed to inhibit mitochondrial cytochrome c release or apoptosis induced by diverse triggers in mammalian cells. These data suggest that the ability to regulate mitochondrial fission/fusion dynamics is an evolutionarily conserved property of the Bcl-2 family.

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Contributors

Author: Patrick J. Duriez

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