Trabd-KO Mouse

TRABD, also known as TraB domain containing, encodes a mitochondrial outer-membrane protein. It plays a crucial role in modulating mitochondrial homeostasis, with its function influencing mitochondrial fusion and fragmentation. It forms complexes with proteins like MFN2, MIGA2, and PLD6, suggesting its involvement in pathways related to mitochondrial dynamics. Understanding TRABD is important for insights into age-related neurodegeneration and certain cancer-related processes [1,2,3].

In flies lacking dTRABD, they are viable with normal lifespans, but aging flies show reduced climbing ability and abnormal mitochondrial morphology in muscles. dTRABD overexpression in fly eyes leads to neurodegeneration and enhances tau toxicity, along with increased reactive oxygen species (ROS), ATP production, and protein turnover in mitochondria, indicating its role in age-related neurodegeneration [1]. In triple-negative breast cancer, ZC3H13-mediated m6A modification reduces doxorubicin resistance by promoting ferroptosis via the KCNQ1OT1/TRABD axis. KCNQ1OT1 enhances the enrichment of H3K4me1/2/3 on the TRABD promoter, increasing its expression [2]. In TNBC cells, STAT3-induced HLA-F-AS1 promotes cell proliferation and stemness characteristics by upregulating TRABD through acting as a molecular sponge of miR-541-3p [3].

In conclusion, TRABD is essential for maintaining mitochondrial homeostasis. Its dysregulation contributes to age-related neurodegeneration as seen in fly models. In cancer, especially triple-negative breast cancer, TRABD is involved in drug resistance and cell proliferation mechanisms, highlighting its significance in these disease areas [1,2,3].

References:

1. Zhou, Caixia, Li, Zhirong, Li, Yawen, Wang, Liquan, Tong, Chao. 2024. TRABD modulates mitochondrial homeostasis and tissue integrity. In Cell reports, 43, 114304. doi:10.1016/j.celrep.2024.114304. https://pubmed.ncbi.nlm.nih.gov/38843396/

2. Huang, Li, Han, Lei, Liang, Shuai, Han, Guohui. 2025. Molecular mechanism of ZC3H13 -mediated ferroptosis in doxorubicin resistance of triple negative breast cancer. In Cell biology and toxicology, 41, 52. doi:10.1007/s10565-024-09980-4. https://pubmed.ncbi.nlm.nih.gov/40000487/

3. Wu, Di, Jia, Hongyao, Zhang, Zhiru, Li, Sijie. 2021. STAT3-induced HLA-F-AS1 promotes cell proliferation and stemness characteristics in triple negative breast cancer cells by upregulating TRABD. In Bioorganic chemistry, 109, 104722. doi:10.1016/j.bioorg.2021.104722. https://pubmed.ncbi.nlm.nih.gov/33618253/