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Inseparable tandem: evolution chooses ATP and Ca2+ to control life, death and cellular signalling.

Helmut Plattner1, Alexei Verkhratsky2

  • 1Department of Biology, University of Konstanz, 78457 Konstanz, Germany helmut.plattner@uni-konstanz.de.

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Summary

Adenosine triphosphate (ATP) and calcium (Ca2+) evolved together, with low intracellular Ca2+ enabling ATP metabolism and Ca2+ signaling. Their interdependent roles in cellular processes and communication highlight a crucial evolutionary success story.

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Area of Science:

  • Evolutionary Biology
  • Cell Biology
  • Biochemistry

Background:

  • Adenosine triphosphate (ATP) is a fundamental energy-storing molecule selected early in evolution.
  • Intracellular calcium (Ca2+) homeostasis was established at low concentrations, enabling its role as a universal signaling molecule.
  • Early eukaryotes developed compartmentalization and vesicle trafficking, utilizing Ca2+ for various cellular functions.

Purpose of the Study:

  • To explore the co-evolutionary relationship between ATP and Ca2+ signaling.
  • To understand how Ca2+ and ATP, despite initial metabolic conflicts, became integrated for complex cellular functions.
  • To elucidate the role of Ca2+ and ATP in the emergence and regulation of eukaryotic cell life and death.

Main Methods:

  • Comparative analysis of evolutionary pathways for ATP metabolism and Ca2+ signaling.
  • Investigation of the biochemical interplay between phosphate metabolism and Ca2+ solubility.
  • Examination of the development of Ca2+ microdomains and their role in cellular regulation.
  • Analysis of the evolution of intercellular communication via ATP and its link to Ca2+ signaling pathways.

Main Results:

  • The necessity of low intracellular Ca2+ for ATP metabolism inadvertently created a background for Ca2+ signaling.
  • Evolutionary adaptations addressed the conflict between Ca2+ and phosphate, leading to spatial and temporal restriction of Ca2+ signals.
  • ATP emerged as a key intercellular messenger, with its effects often mediated by Ca2+-linked purinoceptors.
  • Ca2+ homeostasis became critical for regulating cell survival and death, particularly with the advent of intracellular trafficking.

Conclusions:

  • The seemingly antagonistic relationship between Ca2+ and ATP evolved into a mutually beneficial, interdependent system crucial for eukaryotic cell complexity.
  • Ca2+ and ATP are central to fundamental cellular processes, from energy metabolism and signaling to intercellular communication and cell fate determination.
  • This evolutionary "unholy alliance" underscores the intricate and successful integration of key molecules in driving biological innovation.