Apoo, also known as apolipoprotein O or MIC26, is a constitutive protein of the mitochondrial cristae organizing system complex. It plays a crucial role in regulating lipid metabolism, with implications in multiple biological processes. It is involved in pathways related to mitochondrial function, peroxisomal biogenesis, and cholesterol metabolism, which are vital for maintaining overall physiological homeostasis [1,3,4]. Genetic models, such as knockout (KO) and conditional knockout (CKO) mouse models, have been instrumental in studying Apoo's functions in vivo.

In adipocytes, Apoo-knockout (ApooACKO) mice showed increased adiposity, BAT dysfunction and whitening, reduced non-shivering thermogenesis, and blunted cold responses. Apoo deficiency disrupted mitochondrial structure, impaired oxidative phosphorylation, shifted metabolism from oxidative to glycolytic, increased lipogenic enzyme levels, and promoted BAT whitening. It also inhibited thermogenesis in BAT and disturbed peroxisomal biogenesis via peroxisome proliferator-activated receptor α, aggravating diet-induced obesity [1]. In macrophages, macrophage-specific Apoo knockout (MIC26LysM) mice had smaller atherosclerotic lesions and necrotic cores. Loss of Apoo increased efferocytosis, which was related to abnormal mitochondrial inner membrane structure, increased mitochondrial fission, and decreased mitochondrial membrane potential due to reduced OPA1 [2]. Hepatic Apoo depletion in global knockout (Apoo-/ -) mice aggravated diet-induced obesity and elevated plasma cholesterol levels, affecting cholesterol metabolism independent of LDLR and APOE [3].

In conclusion, Apoo is essential for maintaining normal mitochondrial function, lipid metabolism, and cellular homeostasis. Studies using Apoo KO/CKO mouse models have revealed its significance in obesity-related disorders like brown adipose tissue whitening, diet-induced obesity, and atherosclerosis, providing potential therapeutic targets for these diseases [1,2,3].