期刊
CELL DEATH AND DIFFERENTIATION
卷 30, 期 3, 页码 731-741出版社
SPRINGERNATURE
DOI: 10.1038/s41418-022-01078-w
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The activity and structure of BOK protein, a member of the BCL-2 family, have been investigated. It was found that the thermal stability and pore activity of BOK depend on its C-terminus and the presence of mitochondrial lipid cardiolipin. BOK pores were visualized in liposomes and apoptotic mitochondria, showing similar properties to BAX and BAK. However, BOK's apoptotic activity is limited by its partial mitochondrial localization and is independent of other BCL-2 proteins.
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. BOK-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.
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