Unmasking the Janus face of myoglobin in health and disease.
For more than 100 years, myoglobin has been among the most extensively studied proteins. Since the first comprehensive review on myoglobin function as a dioxygen store by Millikan in 1939 and the discovery of its structure 50 years ago, multiple studies have extended our understanding of its occurrence, properties and functions. Beyond the two major roles, the storage and the facilitation of dioxygen diffusion, recent physiological studies have revealed that myoglobin acts as a potent scavenger of nitric oxide (NO(*)) representing a control system that preserves mitochondrial respiration. In addition, myoglobin may also protect the heart against reactive oxygen species (ROS), and, under hypoxic conditions, deoxygenated myoglobin is able to reduce nitrite to NO(*) leading to a downregulation of the cardiac energy status and to a decreased heart injury after reoxygenation. Thus, by controlling the NO(*) bioavailability via scavenging or formation, myoglobin serves as part of a sensitive dioxygen sensory system. In this review, the physiological relevance of these recent findings are delineated for pathological states where NO(*) and ROS bioavailability are known to be critical determinants for the outcome of the disease, e.g. ischemia/reperfusion injury. Detrimental and beneficial effects of the presence of myoglobin are discussed for various states of tissue oxygen tension within the heart and skeletal muscle. Furthermore, the impact of myoglobin on parasite infection, rhabdomyolysis, hindlimb and liver ischemia, angiogenesis and tumor growth are considered.
Hendgen-Cotta
U B
UB
Department of Medicine, Division of Cardiology, Pulmonary Diseases and Angiology, University Hospital Düsseldorf, Düsseldorf, Germany.
Flögel
U
U
Kelm
M
M
Rassaf
T
T
D000818:Animals; D004194:Disease; D006801:Humans; D008958:Models, Molecular; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009211:Myoglobin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010272:Parasitic Diseases / Q000378:metabolism; D011487:Protein Conformation; D017382:Reactive Oxygen Species / Q000378:metabolism; D051437:Renal Insufficiency / Q000378:metabolism / Q000473:pathology; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology
D009211:Myoglobin; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D010100:Oxygen