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The BCL-2 family saga

Nature Reviews Molecular Cell Biology volume 21, pages 564–565 (2020)Cite this article

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The early 2000s were full of excitement in the cell death field. In particular, several influential studies provided new mechanistic insights into apoptosis, showing that outer mitochondrial membrane permeabilization (MOMP) — considered as the point of no return in apoptosis — is orchestrated by BCL-2 family proteins and that the balance between BCL-2 family members with opposing functions — pro-apoptotic versus pro-survival — defines cell fate. These discoveries spurred a lively debate as to how BCL-2 proteins activate BAX and BAK (family members executing MOMP), with evidence for direct or indirect activation. Complex family business, so to say.

The work of David Andrews and colleagues (Lovell et al.) led a new period in BCL-2 research that focused on reconciling the sequence of events in BCL-2 protein action in apoptosis. Using a minimal system based solely on proteins and membranes, they dissected a series of dynamic events involved in the transformation of soluble, inactive BAX monomers to pore-forming oligomers in the membrane. This study elegantly integrated the direct and indirect activation models of BAX/BAK by BCL-2 proteins and pioneered the idea that the membrane actively regulates the interplay between BCL-2 proteins, adding a new level of regulation to the BCL-2 family affair.

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References

Original articles

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Authors and Affiliations

  1. CECAD Research Center, Institute of Genetics, University of Cologne, Cologne, Germany

    Ana J. García-Sáez

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  1. Ana J. García-Sáez
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Correspondence to Ana J. García-Sáez.

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The author declares no competing interests.

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García-Sáez, A.J. The BCL-2 family saga. Nat Rev Mol Cell Biol 21, 564–565 (2020). https://doi.org/10.1038/s41580-020-0276-2

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