A molecular switch that governs mitochondrial fusion and fission mediated by the BCL2-like protein CED-9 of Caenorhabditis elegans.

Abstract:

:Depending on the cellular context, BCL2-like proteins promote mitochondrial fusion or fission. What determines which of these two opposing processes they promote has so far been unknown. Furthermore, the mechanisms through which BCL2-like proteins affect mitochondrial dynamics remain to be fully understood. The BCL2-like protein CED-9 of Caenorhabditis elegans has previously been shown to promote mitochondrial fusion by physically interacting with the mitochondrial fusion protein FZO-1. Here, we report that CED-9 also physically interacts with the mitochondrial fission protein DRP-1 and that this interaction can be enhanced when CED-9 is associated with the BH3-only protein EGL-1. In addition, we show that the EGL-1-CED-9 complex promotes mitochondrial fission by recruiting DRP-1 to mitochondria and that the egl-1 gene is required for CED-9-dependent mitochondrial fission in vivo. Based on these results, we propose that EGL-1 converts CED-9 into a mitochondrial receptor for DRP-1, thereby shifting its activity from profusion to profission. We hypothesize that BCL2-like proteins act as mitochondrial receptors for DRP-1-like proteins in higher organisms as well and that BH3-only proteins play a general role as modifiers of the function in mitochondrial dynamics of BCL2-like proteins. We speculate that this function of BCL2-like proteins may be as couplers of mitochondrial fusion and fission.

authors

Lu Y,Rolland SG,Conradt B

doi

10.1073/pnas.1103218108

subject

Has Abstract

pub_date

2011-10-11 00:00:00

pages

E813-22

issue

41

eissn

0027-8424

issn

1091-6490

pii

1103218108

journal_volume

108

pub_type

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