A New View of the Lethal Apoptotic Pore

Gorka Basañez, Lucian Soane, J Marie Hardwick

Research output: Contribution to journalArticle

Abstract

Cell death by apoptosis is indispensable for proper development and tissue homeostasis in all multicellular organisms, and its deregulation plays a key role in cancer and many other diseases. A crucial event in apoptosis is the formation of protein-permeable pores in the outer mitochondrial membrane that release cytochrome c and other apoptosis-promoting factors into the cytosol. Research efforts over the past two decades have established that apoptotic pores require BCL-2 family proteins, with the proapoptotic BAX-type proteins being direct effectors of pore formation. Accumulating evidence indicates that other cellular components also cooperate with BCL-2 family members to regulate the apoptotic pore. Despite this knowledge, the molecular pathway leading to apoptotic pore formation at the outer mitochondrial membrane and the precise nature of this outer membrane pore remain enigmatic. In this issue of PLOS Biology, Kushnareva and colleagues describe a novel kinetic analysis of the dynamics of BAX-dependent apoptotic pore formation recapitulated in native mitochondrial outer membranes. Their study reveals the existence of a hitherto unknown outer mitochondrial membrane factor that is critical for BAX-mediated apoptotic pore formation, and challenges the currently popular view that the apoptotic pore is a purely proteinaceous multimeric assembly of BAX proteins. It also supports the notion that membrane remodeling events are implicated in the formation of a lipid-containing apoptotic pore.

Original languageEnglish (US)
Article numbere1001399
JournalPLoS Biology
Volume10
Issue number9
DOIs
StatePublished - Sep 2012

Fingerprint

Mitochondrial Membranes
Membranes
apoptosis
Apoptosis
porins
Porins
Proteins
proteins
Tissue homeostasis
cytochrome c
Cytochromes c
cytosol
Cytosol
cell death
homeostasis
Homeostasis
Cell Death
Deregulation
Cell death
Lipids

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

A New View of the Lethal Apoptotic Pore. / Basañez, Gorka; Soane, Lucian; Hardwick, J Marie.

In: PLoS Biology, Vol. 10, No. 9, e1001399, 09.2012.

Research output: Contribution to journalArticle

Basañez, Gorka ; Soane, Lucian ; Hardwick, J Marie. / A New View of the Lethal Apoptotic Pore. In: PLoS Biology. 2012 ; Vol. 10, No. 9.
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