Cell cycle-dependent regulation of cellular ATP concentration, and depolymerization of the interphase microtubular network induced by elevated cellular ATP concentration in whole fibroblasts

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Abstract
In the present work, evidence is presented indicating that an increased cellular ATP concentration during mitosis may, in conjunction with other factors [Verde et al., 1990: Nature 343:233–238; Andersen et al., 1994: J Cell Biol. 127:1289–1299], induce depolymerization of the interphase microtubular network in cultured fibroblasts. It is shown here that the cellular ATP concentration varies through the cell cycle, reaching a peak at G2M- and minimum at late G1/early S-phase. Furthermore, we have found, using indirect immunofluorescent staining with an antitubulin antibody, that depolymerization of the interphase microtubular network may be induced by increasing the intracellular ATP concentration in cultured fibroblasts from 2.2 mM to 4.1 mM. This may be obtained through addition of adenosine and Pi to the growth medium. Our results indicate that this effect of adenosine and Pi is not mediated via adenosine receptors, but through an elevated cellular ATP concentration. ATP is suggested to act through a concentration-dependent effect on the exchangeable GTP site on tubulin, and not through the action of protein kinases or microtubule-associated proteins.

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