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

Petrina Delivani, Colin Adrain, Rebecca C Taylor, Patrick J Duriez, Seamus J Martin

Research output: Contribution to journalArticlepeer-review

174 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)761-73
Number of pages13
JournalMolecular Cell
Volume21
Issue number6
DOIs
Publication statusPublished - 17 Mar 2006

Keywords

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins/genetics
  • Caenorhabditis elegans/genetics
  • Caenorhabditis elegans Proteins/genetics
  • Cell Line
  • Cricetinae
  • Cytochromes c/metabolism
  • GTP Phosphohydrolases
  • Humans
  • Membrane Proteins/metabolism
  • Mitochondria/metabolism
  • Mitochondrial Proteins/metabolism
  • Proto-Oncogene Proteins/genetics
  • Proto-Oncogene Proteins c-bcl-2/physiology
  • Repressor Proteins/physiology
  • Transfection

Fingerprint

Dive into the research topics of 'Role for CED-9 and Egl-1 as regulators of mitochondrial fission and fusion dynamics'. Together they form a unique fingerprint.

Cite this