FAM3A: a novel mitochondrial protein for the treatment of ischemic diseases

FAM3 metabolism-regulating signaling molecule A (FAM3A) is a mitochondrial protein belonging to the FAM3 gene family with the potential for the treatment of ischemic diseases. FAM3A promotes adenosine triphosphate (ATP) production and improves mitochondrial function by increasing ATP synthase activity and activating the protein kinase B-cyclic AMP-responsive element binding protein-forkhead box D3-ATP synthase regulatory loop, thereby reducing reactive oxygen species production and inhibiting oxidative stress-induced cell death. Additionally, FAM3A activates the nuclear factor erythroid 2-related factor 2 signaling pathway and upregulates the expression of antioxidant proteins, further enhancing the cellular oxidative defense capacity. During angiogenesis, FAM3A positively regulates vascular endothelial growth factor A and promotes endothelial cell migration, proliferation, and tube formation. FAM3A is closely related to atherosclerosis, ischemic encephalopathy, liver ischemia - reperfusion injury, myocardial ischemia, and acute kidney injury. FAM3A plays a role in the course of these diseases via multiple mechanisms, including the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, effectively reducing the inflammatory response and oxidative stress, and influencing disease development. This review comprehensively examines the role of FAM3A in the pathophysiological processes of ischemic diseases across various organs.