Opa1, or Optic atrophy 1, is a mitochondrial dynamin-like GTPase. It has a key role in mitochondrial morphogenesis, regulating inner mitochondrial membrane fusion, cristae remodelling, and mitochondrial energetics [2,4,6]. It is also involved in maintaining mitochondrial DNA and is essential for the dynamic organization and regulation of mitochondria, which are integral for energy metabolism [7]. Genetic models, such as KO/CKO mouse models, have been valuable in studying Opa1's functions.

In gene-knockout studies, human and mouse cells lacking Opa1 are markedly resistant to ferroptosis. Opa1 promotes ferroptosis by maintaining mitochondrial homeostasis and function, contributing to mitochondrial lipid ROS generation and suppressing an ATF4-mediated integrated stress response [1]. In skeletal and cardiac muscle, Opa1 regulates IMM fusion, prevents apoptosis, and is crucial for morphological change in muscle physiology and pathophysiology [2]. In adipocytes, overexpression of Opa1 in mice promotes white adipose tissue browning, improving glucose tolerance and insulin sensitivity [3]. Endothelial Opa1 is required for angiogenesis in a NFκB-dependent pathway, influencing tumor growth and metastatization [5].

In conclusion, Opa1 is essential for mitochondrial function, influencing processes like ferroptosis, muscle function, adipocyte browning, and angiogenesis. The use of Opa1 KO/CKO mouse models has provided insights into its role in these biological processes and associated disease conditions, such as neurodegenerative disorders related to Opa1 mutations [1-3,6,9].