Myoglobin and mitochondria: A relationship bound by oxygen and nitric oxide

Abstract

Since their initial discovery over a century ago, our knowledge of the functions of myoglobin and the mitochondrion has gradually evolved. The mitochondrion, once thought to be solely responsible for energy production, is now known to be an integral redox and apoptotic signal tranducer within the cell. Likewise, myoglobin, traditionally thought of only as an oxygen store, has emerged as a physiological catalyst that can modulate reactive oxygen species levels, facilitate oxygen diffusion and scavenge or generate nitric oxide (NO) depending on oxygen tensions within the cell. By virtue of its unique ability to regulate O2 and NO levels within the cell, myoglobin can modulate mitochondrial function in energy-demanding tissues such as the beating heart and exercising muscle. In this review, we present the conventional functions of myoglobin and mitochondria, and describe how these roles have been reassessed and advanced, particularly in the context of NO and nitrite signaling. We present the mechanisms by which mitochondria and myoglobin regulate one another within the cell through their interactions with NO and oxygen and discuss the implications of these interactions in terms of health and disease.

Myoglobin oxygen affinity in aquatic and terrestrial birds and mammals

“…With decreasing P O2 , the point at which Mb transitions from being a scavenger to a net producer of NO is dependent on the ratio of oxy-Mb to deoxy-Mb and is therefore Mb P 50 dependent (Kamga et al, 2012). Under very hypoxic conditions where the P O2 is below the P 50 of Mb, elevated Mb concentrations in marine mammal muscle may increase this nitrite reductase activity providing increased protection from ischemia reperfusion injury (HendgenCotta et al, 2008;Jensen, 2009) and conserving limited oxygen in ischemic tissues by reducing tissue metabolism (Shiva et al, 2007;Lundberg et al, 2008;Jensen, 2009).…”

Chronic exercise downregulates myocardial myoglobin and attenuates nitrite reductase capacity during ischemia–reperfusion

“…Recently, myoglobin has emerged as a major nitrite reductase in the heart under conditions of ischemia/hypoxia [10, 11]. Myoglobin is a rather interesting monomeric hemoprotein that has been a source of interest to physicians and scientists for almost a century [31, 32]. Classically, the physiological role of myoglobin was attributed to its oxygen storage capacity, but now it is known to be a physiological catalyst that has several cellular functions [32].…”

Monitoring Changes in the Redox State of Myoglobin in Cardiomyocytes by Raman Spectroscopy Enables the Protective Effect of NO Donors to Be Evaluated

“…11 The oxygenated state of myoglobin also acts as a scavenger of cellular NO and, hence, the protein plays a vital role in NO homeostasis, which is particularly important in cardiomyocytes as elevated levels inhibit mitochondrial respiration. 12,13 Non-resonance 14,15 and resonance [16][17][18][19] Raman spectroscopy have been used before in structural imaging of heart tissue 16 and to monitor dynamic changes in both isolated hearts 18 , cardiomyocytes [14][15][16][17] and exposed mitochondria. 19 In our recent work, the cellular mechanisms in ex vivo cardiomyocytes during hypoxia and hyperoxic reoxygenation were studied by Raman spectroscopy using a (non-resonant) excitation wavelength of 488 nm.…”