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Comments to the Paper of A. D. Vinogradov "Myoglobin: What Is It for?"

V. P. Skulachev

Department of Bioenergetics, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119899 Russia; fax: (095) 939-0338; E-mail: skulach@head.genebee.msu.su


And turpentine can be somehow useful.
Koz'ma Prutkov

In his discussion of the work of Garry et al. [1], A. D. Vinogradov suggests two possible explanations for the paradoxical phenomenon that knock-out of the myoglobin gene in mice had no effect on the most essential characteristics of the animals: 1) "more detailed studies might reveal abnormalities that were not detected by the standard physiological tests"; 2) "myoglobin is needed, but not for what are considered to be "text-book" facts" (the transfer of oxygen inside the cell).

In the first case, the reliability of standard physiological tests is questioned, and, in the second case, one of the foundations of our "intellectual cathedral" created to explain events occurring in the living cell through modern biochemistry is destroyed. However, there is a third possibility that was unfortunately mentioned by Garry et al. only as a casual remark at the very end of their manuscript. To avoid the overthrow of routine physiological methods and biochemical dogmas, it is enough to suggest that, apart from myoglobin, there is another unknown redundant mechanism of acceleration of intracellular oxygen transport which functions when myoglobin fails to maintain sufficiently fast rate of O2 transport.

In 1980, S. P. Maslov [2] suggested that an essential biological function is often realized by more than one mechanism. He suggested that this principle is true not only at the macro level (e.g., many organs in animals come in pairs), but also in the case of elementary physiological and biochemical processes. For example, the very efficient yet vulnerable mechanism of respiratory ATP synthesis is paralleled by the less efficient but more reliable glycolytic phosphorylation. Moreover, parallel pathways of electron transfer through the respiratory chain have been described, and they are especially diverse in bacteria. Isozymes may be one more example of this kind. The first complete genome sequencing demonstrated that isozyme diversity is much higher than that described by enzymologists.

The most interesting result of the work of Garry et al. seems to be its indication of the existence of another mechanism for oxygen transport which does not require myoglobin. Such mechanisms are not completely unknown. In the flight muscle of flies, oxygen is delivered directly into mitochondria by microtracheoli. However, the vascular system of the mutant mice is similar to that in normal animals according to the preliminary data of Garry et al. On the other hand, plant cyclosis, i.e., active mixing of the cytoplasm, substituting rapid convection for diffusion of O2 and other water-soluble compounds, might be considered in this context. Moreover, plant chloroplasts seem to have a unique mechanism for mixing of the liquid layers adjacent to the surface of the organelle [3]. A mechanism for cytoplasmic mixing may also be present in cytosol of animal cells or in mitochondria; it may not be so clearly expressed as in the case of plants, but, nevertheless, capable (if stimulated) to solve the problem of O2 delivery when the myoglobin mechanism does not work. It is possible that animal cells or mitochondria lacking myoglobin just mix in some way their cytoplasm. Certainly, this mechanism (unlike myoglobin) must require some energy, but it should be justified when the "free of charge" (myoglobin) pathway of oxygen delivery becomes impossible or insufficient.


REFERENCES

1.Garry, D. J., Ordway, G. A., Lorenz, J. N., Radford, N. B., Chin, E. R., Grange, R. W., Bassel-Duby, R., and Williams R. S. (1998) Nature, 395, 905-908.
2.Maslov, S. P. (1980) in Levels of Organization of Biological Systems (Molchanov, A. M., ed.) [in Russian], Nauka, Moscow, pp. 8-19.
3.Skulachev, V. P. (1988) Membrane Bioenergetics, Springer, Berlin, p. 229.