Bbc3, also known as PUMA (p53 upregulated modulator of apoptosis) and BCL2 binding component 3, is a key pro-apoptotic gene. It plays a significant role in the regulation of cell apoptosis, participating in pathways such as the intrinsic apoptosis pathway [2,5,6]. It is also associated with autophagy-apoptosis interplay, which is crucial in maintaining cellular homeostasis [4,6].

In a mouse miscarriage model, knockdown of murine Bbc3 could efficiently suppress placental apoptosis and alleviate miscarriage, indicating its importance in trophoblast cell apoptosis and miscarriage [1]. In a mouse model of silicosis, Bbc3 knockout mice clearly exhibited decreased levels of autophagy and fibrosis progression, suggesting that Bbc3 in macrophages promotes pulmonary fibrosis development through inducing autophagy during silicosis [2]. In neurons exposed to the organophosphate pesticide chlorpyrifos, Bbc3 loss attenuated CPF-driven neurotoxicity, induction of other intrinsic apoptosis regulatory genes, and cleavage of apoptosis executors. Bbc3 -/- neuronal cultures enhanced the endoplasmic reticulum stress response and upregulated protein clearance mechanisms as a component of resistance to CPF-mediated toxicity [3]. In islet injury mediated by cold preservation and rewarming, Bbc3-KO islets from cold-preserved pancreata showed reduced HMGB1 expression and decreased levels of 4-HNE protein adducts, and higher viability after culture, demonstrating the involvement of Bbc3 in this process [7].

In conclusion, Bbc3 is essential in regulating apoptosis and autophagy in various cell types. Gene-knockout mouse models have revealed its roles in diseases such as miscarriage, silicosis, neurodegenerative diseases related to pesticide exposure, and islet injury during cold preservation and rewarming. These findings provide insights into potential therapeutic strategies for these disease conditions.