Cytoglobin is an evolutionary ancient hemoglobin with poor functional annotation. Rather than constrained to penta coordination, cytoglobin's heme iron may exist either as a penta or hexacoordinated arrangement when exposed to different intracellular environments. Two cysteine residues at the surface of the protein form an intramolecular disulfide bond that regulates iron coordination, ligand binding, and peroxidase activity. Overall, biochemical results do not support a role for cytoglobin as a direct antioxidant enzyme that scavenges hydrogen peroxide because the rate of the reaction of cytoglobin with hydrogen peroxide is several orders of magnitude slower than metal and thiol-based peroxidases. Thus, alternative substrates such as fatty acids have been suggested and regulation of nitric oxide bioavailability through nitric oxide dioxygenase and nitrite reductase activities has received experimental support. Cytoglobin is broadly expressed in connective, muscle, and nervous tissues. Rational for differential cellular distribution is poorly understood but inducibility in response to hypoxia is one of the most established features of cytoglobin expression with regulation through the transcription factor hypoxia-inducible factor (HIF). Phenotypic characterization of cytoglobin deletion in the mouse have indicated broad changes that include a heightened inflammatory response and fibrosis, increase tumor burden, cardiovascular dysfunction, and hallmarks of senescence. Some of these changes might be reversed upon inhibition of nitric oxide synthase. However, subcellular and molecular interactions have been seldom characterized. In addition, specific molecular mechanisms of action are still lacking. We speculate that cytoglobin functionality will extend beyond nitric oxide handling and will have to encompass indirect regulatory antioxidant and redox sensing functions.

细胞红蛋白是一种进化的古老血红蛋白，功能注释较差。当暴露于不同的细胞内环境时，细胞红蛋白的血红素铁可能以五配位或六配位排列的形式存在，而不是受限于五配位。蛋白质表面的两个半胱氨酸残基形成分子内二硫键，调节铁配位、配体结合和过氧化物酶活性。总体而言，生化结果不支持细胞红蛋白作为清除过氧化氢的直接抗氧化酶的作用，因为细胞红蛋白与过氧化氢的反应速率比金属和硫醇基过氧化物酶慢几个数量级。因此，已经提出了诸如脂肪酸的替代底物，并且通过一氧化氮双加氧酶和亚硝酸还原酶活性调节一氧化氮生物利用度已得到实验支持。细胞红蛋白在结缔组织、肌肉组织和神经组织中广泛表达。差异细胞分布的合理性知之甚少，但响应缺氧的诱导性是通过转录因子缺氧诱导因子 (HIF) 调节的细胞红蛋白表达最成熟的特征之一。小鼠细胞红蛋白缺失的表型特征表明存在广泛的变化，包括炎症反应和纤维化增强、肿瘤负荷增加、心血管功能障碍和衰老特征。抑制一氧化氮合酶后，其中一些变化可能会逆转。然而，亚细胞和分子相互作用很少被表征。此外，仍然缺乏具体的分子作用机制。我们推测细胞红蛋白功能将超越一氧化氮处理，并且必须包含间接调节抗氧化和氧化还原传感功能。