Deficiency in Bim, Bid and Bbc3 (Puma) do not prevent axonal injury induced death

Dear Editor,

BAX activation is a critical step in the apoptotic pathway in neurons. BAX activation is multistep process that can be driven by a subset of other pro-apoptotic Bcl-2 family members, specifically the BH3-only proteins BIM, BBC3 (PUMA), and BID.¹ In fact BAX activation appears to require at least one of these pro-apoptotic chaperones during development and after many apoptotic insults.² Retinal ganglion cells (RGCs) die by a BAX-dependent mechanism in development and after axonal injury,³ a key insult in many neurodegenerations. During development BAX-dependent death of RGCs requires BBC3 (Harder and Libby⁴ and Supplementary Figure 1A); however, the molecules controlling BAX activation after axonal injury are unknown. We have previously shown that single deficiency in Bim or Bbc3 lessen early RGC death after axonal injury.^{4, 5} However, by 5 days after injury, RGC death is no longer different in Bbc3-deficient mice and there is a significant number of apoptotic RGCs in Bim-deficient mice (Supplementary Figure 1B). These data show that both BIM and BBC3 are involved in BAX activation in axonally injured RGCs, but are not solely responsible for RGC death.

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