Bola3-KO Mouse

Bola3, short for BolA family member 3, is a gene with significant functions in maintaining mitochondrial homeostasis. It is involved in the iron-sulfur (Fe-S) cluster assembly pathway in mitochondria, which is crucial for the maturation of Fe-S proteins that participate in energy metabolism [1,3,6,7].

Studies have shown that in beige adipocytes, Bola3 deficiency inhibits thermogenesis activity, likely through impairing mitochondrial homeostasis and lipolysis [1]. Mutations in Bola3 can lead to multiple mitochondrial dysfunctions syndrome (MMDS2), as seen in patients with severe leukoencephalopathy, where it affects mitochondrial respiratory chain enzyme activity and protein subunits of mitochondrial complexes [4]. In lung adenocarcinoma, elevated Bola3 expression is associated with poor prognosis and is correlated with tumor immune infiltration [2]. In esophageal squamous cell carcinoma, a long-form Bola3 (Bola3-L) promoted by HNRNPC accelerates cancer progression and is involved in mitochondrial stability [5].

In conclusion, Bola3 is essential for mitochondrial-related functions such as energy metabolism and mitochondrial protein maturation. Its deficiency or mutation can lead to various diseases, including metabolic and neurodegenerative disorders as well as certain cancers. The study of Bola3 through genetic models helps in understanding the underlying mechanisms of these diseases, potentially providing new targets for treatment [1,2,4,5].

References:

1. Bai, Ningning, Ma, Jingyuan, Alimujiang, Miriayi, Bao, Yuqian, Yang, Ying. 2021. Bola3 Regulates Beige Adipocyte Thermogenesis via Maintaining Mitochondrial Homeostasis and Lipolysis. In Frontiers in endocrinology, 11, 592154. doi:10.3389/fendo.2020.592154. https://pubmed.ncbi.nlm.nih.gov/33505355/

2. Wang, Xiao-Fei, Lei, Wei, Liu, Chuan-Mei, Yang, Jie, Zhu, Ye-Han. 2022. BOLA3 is a prognostic-related biomarker and correlated with immune infiltrates in lung adenocarcinoma. In International immunopharmacology, 107, 108652. doi:10.1016/j.intimp.2022.108652. https://pubmed.ncbi.nlm.nih.gov/35286914/

3. Sen, Sambuddha, Thompson, Zechariah, Wachnowsky, Christine, Harvey, Sophie R, Cowan, J A. . Biochemical impact of a disease-causing Ile67Asn substitution on BOLA3 protein. In Metallomics : integrated biometal science, 13, . doi:10.1093/mtomcs/mfab010. https://pubmed.ncbi.nlm.nih.gov/33693876/

4. Stutterd, C A, Lake, N J, Peters, H, Simons, C, Leventer, R J. 2018. Severe Leukoencephalopathy with Clinical Recovery Caused by Recessive BOLA3 Mutations. In JIMD reports, 43, 63-70. doi:10.1007/8904_2018_100. https://pubmed.ncbi.nlm.nih.gov/29654549/

5. Tian, Bo, Bian, Yan, Pang, Yanan, Lin, Han, Wang, Luowei. 2024. Dysregulated inclusion of BOLA3 exon 3 promoted by HNRNPC accelerates the progression of esophageal squamous cell carcinoma. In Frontiers of medicine, 18, 1035-1053. doi:10.1007/s11684-024-1068-4. https://pubmed.ncbi.nlm.nih.gov/39455467/

6. Bargagna, Beatrice, Banci, Lucia, Camponeschi, Francesca. 2023. Understanding the Molecular Basis of the Multiple Mitochondrial Dysfunctions Syndrome 2: The Disease-Causing His96Arg Mutation of BOLA3. In International journal of molecular sciences, 24, . doi:10.3390/ijms241411734. https://pubmed.ncbi.nlm.nih.gov/37511493/

7. Saudino, Giovanni, Suraci, Dafne, Nasta, Veronica, Ciofi-Baffoni, Simone, Banci, Lucia. 2021. Molecular Basis of Multiple Mitochondrial Dysfunctions Syndrome 2 Caused by CYS59TYR BOLA3 Mutation. In International journal of molecular sciences, 22, . doi:10.3390/ijms22094848. https://pubmed.ncbi.nlm.nih.gov/34063696/