Family with sequence similarity 83 A (FAM83A) is a newly discovered proto-oncogene that has been shown to play key roles in various cancers. However, the function of FAM83A in other physiological processes is not well known. Here, we report a novel function of FAM83A in adipocyte differentiation. We used an adipocyte-targeting fusion oligopeptide (FITC-ATS-9R) to deliver a FAM83A-sgRNA/Cas9 plasmid to knockdown Fam83a (ATS/sg-FAM83A) in white adipose tissue in mice, which resulted in reduced white adipose tissue mass, smaller adipocytes, and mitochondrial damage that was aggravated by a high-fat diet. In cultured 3T3-L1 adipocytes, we found loss or knockdown of Fam83a significantly repressed lipid droplet formation and downregulated the expression of lipogenic genes and proteins. Furthermore, inhibition of Fam83a decreased mitochondrial ATP production through blockage of the electron transport chain, associated with enhanced apoptosis. Mechanistically, we demonstrate FAM83A interacts with casein kinase 1 (CK1) and promotes the permeability of the mitochondrial outer membrane. Furthermore, loss of Fam83a in adipocytes hampered the formation of the TOM40 complex and impeded CK1-driven lipogenesis. Taken together, these results establish FAM83A as a critical regulator of mitochondria maintenance during adipogenesis.

具有序列相似性的家族 83 A (FAM83A) 是一种新发现的原癌基因，已被证明在多种癌症中发挥关键作用。然而，FAM83A 在其他生理过程中的功能并不为人所知。在这里，我们报告了 FAM83A 在脂肪细胞分化中的新功能。我们使用脂肪细胞靶向融合寡肽 (FITC-ATS-9R) 传递 FAM83A-sgRNA/Cas9 质粒以敲低小鼠白色脂肪组织中的Fam83a (ATS/sg-FAM83A)，从而减少白色脂肪组织质量，更小的脂肪细胞，以及因高脂肪饮食而加剧的线粒体损伤。在培养的 3T3-L1 脂肪细胞中，我们发现Fam83a丢失或敲低显着抑制脂滴形成并下调脂肪生成基因和蛋白质的表达。此外，抑制Fam83a通过阻断电子传递链减少线粒体 ATP 的产生，这与增强的细胞凋亡有关。从机制上讲，我们证明 FAM83A 与酪蛋白激酶 1 (CK1) 相互作用并促进线粒体外膜的通透性。此外，脂肪细胞中Fam83a的缺失阻碍了 TOM40 复合物的形成，并阻碍了 CK1 驱动的脂肪生成。综上所述，这些结果确立了 FAM83A 作为脂肪生成过程中线粒体维持的关键调节因子。