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. Author manuscript; available in PMC: 2020 Jul 1.
Published in final edited form as: Clin Cancer Res. 2019 Apr 5;25(13):3776–3783. doi: 10.1158/1078-0432.CCR-18-1909

Figure 5: Mitochondrial Priming.

Figure 5:

DNA damaging (orange) or proteasome inhibiting (blue) drugs illicit apoptosis signaling through select member(s) of BH3-only pro-apoptotic protein family (BIM, NOXA (blue), PUMA, BAD, HRK (orange), BID, and MS-1). These proteins then carry the apoptosis signal to mitochondria, where they impact the free pool of effector pro-apoptotic proteins. When dissociated from anti-apoptotic proteins, the effector proteins cause mitochondrial outer membrane permeabilization (MOMP) triggering the mitochondrial apoptosis signal. In this assay, BH3-only mimetic peptides artificially reproduce this signaling pathway and the MOMP signal from the drug associated BH3 only protein is subsequently analyzed. The extent of MOMP is measured by flow cytometry using a mitochondrial potentiometric dye, JC-1. Thus, BH3 profiling surveys how likely the drugs are to complete the apoptotic signal. This was performed in ex vivo experiments at pretreatment as described previously.