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- W3004804045 abstract "The Bcl-2 associated X protein, BAX, induces mitochondrial outer membrane permeability (MOMP) leading to cytochrome c release. BAX also interacts with complex I of the electron transport chain and suppresses ROS generation, particularly in cancer cells. To further delineate these multi-modal effects of BAX, we investigated 1) the impact of BAX on mitochondrial bioenergetics under different substrate conditions and 2) the ability of BAX to induce lipidic pores and/or proteinaceous channels. The effects of BTSA1, a potent activator of BAX, were also investigated. Mitochondria isolated from rat hearts were energized with either complex I substrate Na-pyruvate malate (PM) or complex II substrate Na-succinate (Suc). Our results show that BTSA1, in the absence or presence of exogenous BAX, increased the rate of mitochondrial O2 consumption in both PM- and Suc-energized mitochondria. BAX increased the rate of ROS production in PM-energized mitochondria, whereas BTSA1, with or without addition of BAX, decreased the rate of ROS production in Suc-energized mitochondria. Addition of BAX depolarized PM- and Suc-energized mitochondria and BTSA1, with or without BAX, hyperpolarized PM-energized mitochondria. The molecular mechanism of BAX-induced MOMP was investigated by monitoring membrane integrity using planar lipid bilayer electrophysiology. We found that bilayer disruption occurred via 1) gradual increase in current across the bilayer with ion channel-like activity and 2) instantaneous increase in current indicative of lipid bilayer breakdown. BTSA1 significantly enhanced both these effects. Our studies show that BAX may increase or decrease mitochondrial ROS production in a substrate-dependent manner and this differential effect may involve complex II. The formation of both lipidic pores and proteinaceous channels are possible and are not mutually exclusive. Additional experiments are needed to identify factors leading to these different formations." @default.
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- W3004804045 date "2020-02-01" @default.
- W3004804045 modified "2023-09-27" @default.
- W3004804045 title "Multi-Modal Actions of BAX and BTSA1 on Mitochondrial Bioenergectics and Membrane Integrity" @default.
- W3004804045 doi "https://doi.org/10.1016/j.bpj.2019.11.2507" @default.
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