Atg7, an essential autophagy-related gene, acts as an E1-like activating enzyme. It is crucial for classical degradative macroautophagy/autophagy, facilitating both microtubule-associated protein light chain 3 (LC3)-phosphatidylethanolamine and ATG12 conjugation. Thus, it stands at the hub of two ubiquitin-like systems in autophagic vesicle expansion. It is also involved in regulating cell cycle, apoptosis, immunity, and protein secretion, and plays a significant role in human health and disease [6,7].

In adipose-selective fto knockout mice, FTO deficiency decreased white fat mass and impaired ATG7-dependent autophagy in vivo, indicating that m6A mRNA methylation controls autophagy and adipogenesis by targeting Atg7 [1]. In Chk2-/-mice, an aggravated infarction phenotype was observed along with reduced phosphorylation of TRIM32 and ubiquitination of ATG7 in a stroke model, suggesting that the ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initiate autophagy under oxidative stress [2]. Endothelial cell-specific atg7 knockout (atg7 KO) mice showed impaired angiogenesis, delayed blood flow reperfusion, and reduced HIF1A expression, revealing that lack of ATG7 inhibits angiogenesis by suppressing HIF1A expression through upregulating STAT1 independently of autophagy under ischemic conditions [3]. TRIM7-deficient mice had elevated innate immune responses and increased L. monocytogenes infection, as TRIM7 promotes autophagy via regulation of ATG7 ubiquitination during infection [4]. Conditional knockout of Atg7 in endothelial cells (Atg7-ECKO) led to astrocyte-microvascular disassociation and BBB leakage in mice, suggesting that endothelial Atg7 is essential for maintaining BBB integrity [5].

In conclusion, Atg7 is a key regulator in multiple biological processes. Gene knockout and conditional knockout mouse models have been instrumental in uncovering its role in autophagy, adipogenesis, angiogenesis, oxidative stress response, anti-bacterial defense, and blood-brain barrier maintenance. These findings contribute to understanding the mechanisms underlying various diseases such as obesity, stroke, ischemic diseases, intracellular bacterial infections, and potentially neurological disorders related to BBB dysfunction.