Depletion of BAK Affects Emission of Reactive Oxygen Species from Mitochondria

Abstract

Research in the past 15 years has established roles for the pro-apoptotic proteins Bax and Bak in release of death signaling molecules from mitochondria. The process involves relocation of cytoplasmic Bax into the mitochondrial outer membrane to form a giant pore, MAC. The other MAC component, Bak, is constitutively present in the outer membrane regardless of apoptotic stimulation. In this study we investigated the role of Bak in mitochondrial function outside the context of apoptosis. We examined the effects of Bak elimination on emission of reactive oxygen species from mitochondria. Our results indicate a disturbance of free-radical production both in cultured mouse embryonic fibroblasts and in isolated mitochondria. These changes were not observed in mitochondria lacking the pro-apoptotic Bax protein. Our future studies will verify if these effects are independent from apoptotic roles of Bak and examine a possible functional interaction between Bak and the respiratory complexes in mitochondria.