About the logo

Any Darwin aficionado probably recognized that the phylogenetic tree running over the mitochondrion was directly inspired by Darwin's tree of life as drawn in his sketchbook (Transmutation of Species, 1837).

A former version of the BCL2DB logo was a hand-drawn image of a card figuring The Chariot, the seventh major arcana of the Tarot of Marseille, as reconstituted by Philippe Camoin and Alexandro Jodorowsky (see more here). Although we made substantial changes to the original material, our logo was deemed by the copyright owners to resemble too much to their creation so we could not get permission to use it on this website. Because we have found this trump to be an interesting mirror or symbolic reflection of BCL-2 family-regulated apoptosis, we decided to offer here the accompanying text, which has been written by Abdel Aouacheria. Ready for an anti-psychic, highly subjective and BCL-2 family-oriented interpretation of the Chariot?

The card can be read much like an integrated map depicting the various subgroups forming the BCL-2 group of proteins, their molecular functions and the biological processes they are involved in. Having in mind that artistic reading of the Tarot has nothing to do with science, but at the same time is not necessarily incompatible with it, in the following paragraphs, I invite the reader to share (and hopefully to review and extend) some of the thoughts that came to me while examining this card.

A line divides the 7th card of the Tarot into two halves. The top part of the image deals with BH3-only proteins and the bottom half with BCL-2 homologous proteins. Let's start by examining the bottom part. The two horses pulling the Chariot symbolize respectively the anti-apoptotic and pro-apoptotic BCL-2 homologs. These proteins are homologous in the phylogenetic sense, i.e., they derive from a common ancestor (the horses are conjoined twins, who share their two legs). The right horse, which corresponds to the anti-apoptotic clan, has a ruptured eye, consistent with the idea that pro-survival BCL-2 homologs, contrary to their pro-apoptotic relatives BAX and BAK, may not be able to form oligomers that perforate the mitochondrial outer membrane. A mitochondrion is apparent in the background, where the Chariots wheels are drawn. The rim is reminiscent of the double membrane structure and the spokes is reminiscent of the cristae. The mitochondrial membrane located on the left side exhibits small dots that represent the pores through which cytochrome c and other mitochondrial proteins are released during apoptosis, whereas the membrane on the opposite side of the image (where the "anti-apoptotic" horse is) appears intact. The growing plants can be viewed as an allegory of the energy produced by the mitochondria and which is used by the cell to perform its life processes.

The BCL-2/BAX mitochondrial checkpoint of apoptosis is controlled by BH3-only proteins which are personified by the chariot driver, shown in the upper half of the picture. The charioteer is a prince who wears a crown and holds a wand in his right hand; these elements are symbols of power, which fits well with the upstream position of BH3 proteins in apoptotic signaling. This power is under tight control, as evidenced by the prince's left arm that seems to be attached to the pillar behind. The prince harbors two faces on his spaulders. The faces are not symmetrical (equivalent) and represent the two classes of BH3-only members: activators and sensitizers. The different types of BCL-2 homologs share a similar structural fold: they are folded into a globular shape, and were therefore embodied in readily identifiable animals (horses). In contrast, a number of BH3-only members are intrinsically disordered proteins: they lack a fixed and rigid fold (a "body") and are defined by their action mode or by sequence signatures ("faces"). The small rivets in the costume of the prince evoke the numerous BH3 mimetics (like ABT-737) developed to mimic the function of BH3-only proteins. It is interesting to notice that the cranium of the charioteer is incomplete: the character symbolizing the BH3 subfamily is not an absolute sovereign; his authority is limited and is influenced by pro-apoptotic signals, which are represented by the overhanging canopy of stars. The pillars are reminiscent of the lines and arrows classically used to link elements in cell signaling diagrams, indicating that a mechanistic "intelligence" (signal transduction pathways) controls the decision to organize or disorganize the matter, i.e., to induce mitochondrial membrane permeabilization and cell death. In the Tarot deck, the bottom band generally contains the card name. The Chariot is the only major arcana for which a period can be found at the end of the word "CHARIOT." (hereby replaced by "The BCL-2 Family."), carrying the meaning of irrevocable change (like apoptosis, which is irreversible cellular demise).

There is a peculiar item in the center of the coat of arms, between the horses: a drop, which symbolizes immortality, or the ability to sustain life. One way to make sense of this is to acknowledge that life and death are "two sides of the same coin". This perspective has been corroborated by recent studies, which have found that BCL-2 family members were not only involved in apoptosis control but also exert important functions in cells uncommitted to death. While these non-apoptotic roles of BCL-2 family proteins are already suggested by the two-wheeled horse-drawn vehicle, they will be hopefully addressed in the future by reading another major arcana card, intimately related to the Chariot: the Star (trump #17).