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BOK is a poorly understood member of the BCL-2 family of proteins that has been proposed to function as a pro-apoptotic, BAX-like effector. However, the molecular mechanism and structural properties of BOK pores remain enigmatic. Here, we show that the thermal stability and pore activity of BOK depends on the presence of its C-terminus as well as on the mitochondrial lipid cardiolipin. We directly visualized BOK pores in liposomes by electron microscopy, which appeared similar to those induced by BAX, in line with comparable oligomerization properties quantified by single molecule imaging. In addition, super-resolution STED imaging revealed that BOK organized into dots and ring-shaped assemblies in apoptotic mitochondria, also reminiscent of those found for BAX and BAK. Yet, unlike BAX and BAK, the apoptotic activity of BOK was limited by partial mitochondrial localization and was independent of and unaffected by other BCL-2 proteins. These results suggest that, while BOK activity is kept in check by subcellular localization instead of interaction with BCL-2 family members, the resulting pores are structurally similar to those of BAX and BAK.Bullet pointsBOK-induced pores were directly visualized in liposomes using negative staining EM.BOK apoptotic activity is comparable to and independent of BAX and BAK, including formation of rings in apoptotic mitochondria.Apoptosis induction by BOK is limited by partial mitochondrial localization.

Purpose The present study aimed to develop, statistically optimize, and characterize hydroquinone-loaded transfersomes (HQ-TFs) for effective topical delivery by mitigating the problems associated with HQ. Methods HQ-TFs were prepared by the thin-film hydration method and characterized for particle size, zeta potential (ZP), entrapment efficiency (EE), in vitro drug release, and skin penetration potential. The optimized hydroquinone-loaded transfersome (OPT-HQ-TF) was incorporated in a gel and evaluated for ex vivo skin permeation and deposition profile, in vitro antioxidant activity, in vitro cytotoxicity study, in vitro tyrosinase inhibition assay, and dermal skin irritation study. Results The OPT-HQ-TF showed a particle size of 210 nm, ZP of − 15.10 mV, and EE% of 67.61. The cumulative drug release % from transfersomal formulations ranged from 54.39 ± 1.92 to 76.05 ± 1.18%. The fluorescence microscopy investigation revealed the penetration of transfersomes into deeper skin layers. The skin permeation and deposition studies indicated that the OPT-HQ-TF gel improved permeation and drug retention in the skin compared to the HQ plain gel. The antioxidant assay revealed that HQ retained its antioxidant activity after encapsulation. The cytotoxicity study demonstrated that the OPT-HQ-TF gel significantly decreased the cytotoxicity towards L-929 mouse fibroblast. The tyrosinase inhibition assay specified that the OPT-HQ-TF gel has the potential to treat hyperpigmentation. The dermal skin irritation study indicated that the OPT-HQ-TF gel is safe and non-irritant. Conclusion The present study findings suggested the potential application of deformable nanovesicles as an innovative topical drug delivery system of HQ in the treatment of hyperpigmentation.