Is Intracellular ph a Master Clock for the Events of Mitosis?

Abstract

Experiments have shown that the intracellular pH of many cell types rises to a maximum at the onset of mitosis, subsequently decreasing 0.3 to 0.5 pH units from typical peak values of 7.3 to 7.5 measured during prophase [1]. This result, and observations that tubulin net charge depends strongly on pH, varying quite linearly from −12 to −28 (electron charges) between pH 5.5 and 8.0 [2,3], could be significant for microtubule (MT) dynamics during mitosis. Studies have shown that MT dynamics is sensitive to pH, with MT growth favored by higher intracellular pH values [4-6]. Given the above observations collectively, it seems reasonable to assume that the shift from the dominance of MT growth during prophase, and to a lesser extent during prometaphase, to a parity between MT polymerization and depolymerization during metaphase chromosome oscillations could be attributed to the gradual downward intracellular pH shift during mitosis that is observed in many cells. Thus the timing and sequencing of prophase, prometaphase, and metaphase chromosome motions may be understood as an increase in the MT disassembly to assembly probability ratio resulting from a continuously falling intracellular pH [7,8]. [1] See for ex., Amirand, C. et al., Biol. Cell, vol. 92:409 (2000). [2] Sackett, D., Banff Workshop, Molecular Biophysics of the Cytoskeleton, Banff, Alberta, Canada, Aug. 25-30, 1997. [3] Tuszynski, J.A. et al., J. Theor. Biol., vol. 174:371 (1995). [4] Schatten, G. et al., Eur. J. Cell Biol., vol 36:116 (1985). [5] Kirschner, M.W., J. Cell Biol., vol.88:604 (1980). [6] Deery, W.J. and Brinkley, B.R., J. Cell Biol., vol. 96:1631 (1983). [7] Gagliardi, L.J., Phys. Rev. E 66:011901 (2002). [8] Gagliardi, L.J. “Electrostatic Considerations in Mitosis”, iUniverse Publishing Co., 2009.