ATF5, a putative therapeutic target for the mitochondrial DNA 3243A > G mutation-related disease

Abstract The mitochondrial DNA m.3243A > G mutation is well-known to cause a variety of clinical phenotypes, including diabetes, deafness, and osteoporosis. Here, we report isolation expansion urine-derived stem cells (USCs) from patients carrying the mutation, which demonstrate bimodal heteroplasmy. USCs with high levels displayed abnormal morphology function, as well elevated ATF5-dependent unfolded protein response (UPR mt ), together reduced Wnt/β-catenin signaling osteogenic potentials. Knockdown ATF5 in mutant suppressed UPR , improved restored expression GSK3B WNT7B rescued These results suggest that could be core disease mechanism underlying dysfunction osteoporosis related therefore novel putative therapeutic target for this genetic disorder.