International Society for History, Philosophy, and Social Studies of Biology

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MONDAY, JULY 6  /  19:00 - 20:30  /  Salle Marie Gérin-Lajoie
From dualism to multiplicity: seeing Bcl-2 family proteins and cell death with new eyes

Abdel Aouacheria (CNRS/ENS-Lyon, France); Gustave Theilhaber (CNRS/ENS-Lyon, France)

Bcl-2 homologous proteins are extensively studied in cell and medical biology, as they represent essential regulators of the mitochondrial apoptotic pathway in metazoans. Their function is usually given as either pro-apoptotic or anti-apoptotic: an asymmetry in function. Nonetheless, these functionally opposed proteins find their origin in a single ancestor. As testament to this fact, they have maintained a strikingly similar tertiary structure over the course of evolution. We ask how a single protein ancestor could be the originator of homologs having diametrically opposed functions. We also assess if functional divergence reflects at the structural level through some topological asymmetry. Furthermore, some empirical evidence support the notion that certain Bcl-2 homologs are bifunctional, depending on changes in the expression level, alternative splicing and post-translational modifications. Thus, the difference between pro- and anti-apoptotic Bcl-2 proteins may not be a solid dichotomy. To what extent are our understandings of the Bcl-2-regulated pathway dependent on a perceived dichotomy? Recent discoveries found Bcl-2 homologs can display non-mitochondrial and even non-apoptotic roles, suggesting that these proteins are pleiotropically involved in a variety of cell processes. A deeper understanding of the concerned biology can be attained by moving beyond contrasting descriptions towards integrating the evolutionary history and peculiarities the proteins exhibit. The case of the Bcl-2 family might help us reconsider the way we model and define complex biological systems expressing an either/or relationship.