Bcl-2

Bcl-2 (B-cell lymphoma 2) is a central anti-apoptotic regulator that preserves mitochondrial integrity by preventing mitochondrial outer membrane permeabilization (MOMP), a critical checkpoint controlling cytochrome c release and caspase activation during intrinsic apoptosis^[1][2]. Mechanistically, Bcl-2 functions through direct interactions with pro-apoptotic BCL-2 family proteins, including Bax and Bak, thereby suppressing their oligomerization and limiting mitochondrial membrane disruption^[3][4]. The protein also integrates signals transmitted by BH3-only proteins, which regulate the balance between cell survival and programmed cell death under physiological and pathological stress conditions^[3][5]. Dysregulated Bcl-2 expression contributes to apoptosis resistance in multiple malignancies and supports tumor cell survival by maintaining mitochondrial homeostasis despite cellular stress^[6][7]. In disease models, the anti-apoptotic activity of Bcl-2 is closely linked to mitochondrial apoptosis pathways that represent major therapeutic targets in hematologic and solid cancers^[6][8]. Compared with related anti-apoptotic isoforms such as Mcl-1 and Bcl-B, Bcl-2 displays broader interactions with both Bax and Bak, whereas Mcl-1 and Bcl-B show preferential regulation of Bak- and Bax-dependent apoptotic pathways, respectively^[4]. For experimental applications, BH3-mimetic inhibitors disrupt the interaction between Bcl-2 and pro-apoptotic partners, thereby restoring mitochondrial apoptosis and providing a widely used strategy for mechanistic studies and targeted cancer research^[7][8].