Deciphering the mysteries of myoglobin in striated muscle

Myoglobin (Mb) is a large protein that reversibly binds oxygen in the muscl e cell and is thought to be critical for O-2 supply to the mitochondria dur ing 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 P O2 in the cell to prevent mitochondrial anoxia; and (3) parallel diffusion of O-2 (so-called, 'facilitated diffusion'). The storage role is well estab lished in diving mammals and buffering of cell PO2 above anoxic levels is s hown here by in vivo magnetic resonance spectroscopy (MRS). However, the qu antitative role of Mb in 'facilitated' or parallel diffusion of O-2 is cont roversial. Evidence in support of this role is from MRS analyses, which rev eal rapid Mb desaturation with exercise, and from the proportionality of Mb content of a muscle to the O-2 diffusion limitation. Recent experiments wi th myoglobin knockout mice demonstrating high levels of aerobic function in normal and myoglobin-free mice argue against a link between Mb and oxidati ve phosphorylation. Thus, the current evidence supports the role of Mb in t he physical diffusion of O-2; however, the unimpaired aerobic function of M b knockout mice indicates that this role may not be critical to O-2 supply in active muscle.