Activated PGC-1α cooperates with NRF1/2 to upregulate TFAM expression [39], promoting the replication of mitochondrial DNA (mtDNA) and protein synthesis through the PGC-1α-NRF1/2-TFAM pathway, ultimately facilitating mitochondrial biogenesis and alleviating depression [14,40]. Here, NRF1 is linked to major depressive disorder.