Slc25a5-KO Mouse

Slc25a5, also known as solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 5 or ANT2, is a critical inner mitochondrial membrane protein. It functions as a carrier for metabolites, playing a key role in mitochondrial energy metabolism, such as ATP production [2,5]. It is involved in pathways like PINK1-PRKN-dependent mitophagy [2]. Genetic models can be used to study its function and impact on biological processes and diseases.

In colon cancer, Slc25a5 was downregulated, and its upregulation was related to better overall survival. It attenuated cell proliferation, upregulated programmed cell death-related signatures, and inhibited the MAPK signaling pathway [1]. In diabetes-induced osteopenia, BK channels regulated Slc25a5-mediated mitophagy in osteoblasts [2]. In adipogenesis in OP9 cells, depletion of Slc25a5 suppressed adipogenesis-related genes, triglyceride accumulation, and PPARγ protein expression, and reduced oxidative phosphorylation and ATP production, potentially mediated by ERK1/2 phosphorylation [3]. In neuroblastoma, high expression of Slc25a5 predicted poor patient prognosis, and inhibiting it with PENAO reduced cell viability. The combination of PENAO and the histone deacetylase inhibitor SAHA synergistically reduced cell viability and induced apoptosis in neuroblastoma cells [4].

In summary, Slc25a5 is crucial for mitochondrial-related functions like energy metabolism and mitophagy. Its study through model-based research has revealed its role in diseases such as colon cancer, diabetes-induced osteopenia, adipogenesis-related obesity, and neuroblastoma, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Chen, Yan-Jie, Hong, Wei-Feng, Liu, Meng-Ling, Liu, Tian-Shu, Liang, Li. 2022. An integrated bioinformatic investigation of mitochondrial solute carrier family 25 (SLC25) in colon cancer followed by preliminary validation of member 5 (SLC25A5) in tumorigenesis. In Cell death & disease, 13, 237. doi:10.1038/s41419-022-04692-1. https://pubmed.ncbi.nlm.nih.gov/35288533/

2. Jiang, Lan, He, Haidong, Tang, Yuyan, Cai, Hui, Zhang, Xuemei. 2024. Activation of BK channels prevents diabetes-induced osteopenia by regulating mitochondrial Ca2+ and SLC25A5/ANT2-PINK1-PRKN-mediated mitophagy. In Autophagy, 20, 2388-2404. doi:10.1080/15548627.2024.2367184. https://pubmed.ncbi.nlm.nih.gov/38873928/

3. Zhu, Shenglong, Wang, Wei, Zhang, Jingwei, Jing, Zhe, Chen, Yong Q. 2022. Slc25a5 regulates adipogenesis by modulating ERK signaling in OP9 cells. In Cellular & molecular biology letters, 27, 11. doi:10.1186/s11658-022-00314-y. https://pubmed.ncbi.nlm.nih.gov/35109789/

4. Seneviratne, Janith A, Carter, Daniel R, Mittra, Rituparna, Cheung, Belamy B, Marshall, Glenn M. 2022. Inhibition of mitochondrial translocase SLC25A5 and histone deacetylation is an effective combination therapy in neuroblastoma. In International journal of cancer, 152, 1399-1413. doi:10.1002/ijc.34349. https://pubmed.ncbi.nlm.nih.gov/36346110/

5. Le, Jiamei, Chen, Yilong, Yang, Wei, Chen, Ligong, Ye, Jianping. 2023. Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus. In Acta pharmaceutica Sinica. B, 14, 437-454. doi:10.1016/j.apsb.2023.09.004. https://pubmed.ncbi.nlm.nih.gov/38322335/