Deciphering the mysteries of myoglobin in striated muscle

Myoglobin (Mb) is a large protein that reversibly binds oxygen in the muscle cell and is thought to be critical for O-2 supply to the mitochondria during exercise. The role of Mb in aerobic function is evaluated based on the physical properties of Mb as an O-2 carrier and experimental evidence of Mb function in vivo. This role depends on the reversible binding of O-2 by Mb depending on PO2, which results in: (1) storage of O-2; (2) buffering of PO2 in the cell to prevent mitochondrial anoxia; and (3) parallel diffusion of O-2 (so-called, 'facilitated diffusion'). The storage role is well established in diving mammals and buffering of cell PO2 above anoxic levels is shown here by in vivo magnetic resonance spectroscopy (MRS). However, the quantitative role of Mb in 'facilitated' or parallel diffusion of O-2 is controversial. Evidence in support of this role is from MRS analyses, which reveal rapid Mb desaturation with exercise, and from the proportionality of Mb content of a muscle to the O-2 diffusion limitation. Recent experiments with myoglobin knockout mice demonstrating high levels of aerobic function in normal and myoglobin-free mice argue against a link between Mb and oxidative phosphorylation. Thus, the current evidence supports the role of Mb in the physical diffusion of O-2; however, the unimpaired aerobic function of Mb knockout mice indicates that this role may not be critical to O-2 supply in active muscle.