Tfam-flox Mouse

TFAM, also known as transcription factor A, mitochondrial, is a key transcription factor crucial for maintaining mitochondrial DNA (mtDNA) stabilization and initiating its replication [4]. It plays an essential role in cellular bioenergetics, as it is involved in mtDNA maintenance and expression, which is vital for cell survival [5]. TFAM is associated with pathways like autophagy, inflammation, and cGAS-STING pathway, and its function is studied using genetic models.

In multiple disease-related studies, TFAM shows significant impacts. In ischemic acute kidney injury, mitochondrial ROS (mtROS) promotes injury by suppressing TFAM-mediated mtDNA maintenance, while decreasing mtROS levels can reverse TFAM and mtDNA copy number decrease, suggesting TFAM could be a target for renal repair [1]. In alcoholic steatohepatitis, ATF4 activation promotes hepatic mitochondrial dysfunction by repressing NRF1-TFAM signalling, and TFAM overexpression can attenuate alcohol-induced mitochondrial dysfunction and liver damage [2]. In liver cancer, TFAM loss induces nuclear actin assembly upon mDia2 malonylation, promoting metastasis, and TFAM downregulation in metastatic tissues is associated with patient survival [3]. In dendritic cells, TFAM deficiency leads to mitochondrial dysfunction, mtDNA cytosolic leakage, cGAS-STING pathway activation, enhanced antigen presentation, and inhibition of tumor growth [4]. In esophageal squamous cell carcinoma (ESCC), TFAM downregulation promotes autophagy and ESCC survival through mtDNA stress-mediated STING pathway [6].

In conclusion, TFAM is essential for mitochondrial function and mtDNA maintenance. Gene-knockout models in mice have revealed its significant roles in various disease conditions such as kidney injury, liver diseases, cancer metastasis, and antitumor immunity. Understanding TFAM's functions through these models provides insights into disease mechanisms and potential therapeutic targets.