Bcl2l13-KO Mouse

BCL2L13, a BCL2-like protein, has been studied for about two decades and is emerging as a research hotspot. It anchors in the mitochondrial outer membrane, expresses in various cells and tissues, and is involved in multiple processes. It cannot be simply classified as a pro-or anti-apoptotic protein as it can induce mitochondrial fragmentation, inhibit cell death, promote mitophagy, and is associated with growth, development, energy metabolism [1].

In glioblastoma, BCL2L13 expression is upregulated. It targets DNM1L at the Ser616 site, leading to mitochondrial fission and high mitophagy flux, which promotes the proliferation and invasion of glioblastoma cells both in vitro and in vivo, suggesting it as a candidate molecular target for treating glioblastoma [2]. In zebrafish, loss of Bcl2l13 impairs skeletal muscle structure and function, alters Ca2+ signaling, and decreases mitochondrial complexes activity. In mammalian cells, BCL2L13 is present at mitochondria, ER, and mitochondria-associated membranes, and its knockdown in C2C12 cells changes cytosolic Ca2+ release and mitochondrial Ca2+ uptake, indicating its role in maintaining proper skeletal muscle function through Ca2+ signaling [3].

In conclusion, BCL2L13 is crucial for multiple biological processes. Its functions in promoting mitophagy in glioblastoma and maintaining skeletal muscle function through Ca2+ signaling regulation are significant. Research on BCL2L13, especially through gene-knockout or conditional-knockout models as seen in zebrafish, helps in understanding its role in specific disease conditions like glioblastoma, providing potential targets for treatment.

References:

1. Meng, Fei, Sun, Naitong, Liu, Dongyan, Xiao, Jun, Dai, Haiming. 2020. BCL2L13: physiological and pathological meanings. In Cellular and molecular life sciences : CMLS, 78, 2419-2428. doi:10.1007/s00018-020-03702-9. https://pubmed.ncbi.nlm.nih.gov/33201252/

2. Wang, Jiwei, Chen, Anbin, Xue, Zhiwei, Wang, Xinyu, Huang, Bin. 2023. BCL2L13 promotes mitophagy through DNM1L-mediated mitochondrial fission in glioblastoma. In Cell death & disease, 14, 585. doi:10.1038/s41419-023-06112-4. https://pubmed.ncbi.nlm.nih.gov/37660127/

3. Grepper, Dogan, Tabasso, Cassandra, Zanou, Nadège, Fajas, Lluis, Amati, Francesca. 2024. BCL2L13 at endoplasmic reticulum-mitochondria contact sites regulates calcium homeostasis to maintain skeletal muscle function. In iScience, 27, 110510. doi:10.1016/j.isci.2024.110510. https://pubmed.ncbi.nlm.nih.gov/39175772/