Neuroglobin and cytoglobin: Fresh blood for the vertebrate globin family

Neuroglobin and cytoglobin are two recently discovered members of the vertebrate globin family. Both are intracellular proteins endowed with hexacoordinated heme‐Fe atoms, in their ferrous and ferric forms, and display O 2 affinities comparable with that of myoglobin. Neuroglobin, which is predominantly expressed in nerve cells, is thought to protect neurons from hypoxic–ischemic injury. It is of ancient evolutionary origin, and is homologous to nerve globins of invertebrates. Cytoglobin is expressed in many different tissues, although at varying levels. It shares common ancestry with myoglobin, and can be traced to early vertebrate evolution. The physiological roles of neuroglobin and cytoglobin are not completely understood. Although supplying cells with O 2 is the likely function, it is also possible that both globins act as O 2 ‐consuming enzymes or as O 2 sensors. Here, we review what is currently known about neuroglobin and cytoglobin in terms of their function, tissue distribution and relatedness to the well‐known hemoglobin and myoglobin. Strikingly, the data reveal that O 2 metabolism in cells is more complicated than was thought before, requiring unexpected O 2 ‐binding proteins with potentially novel functional features.