Abstract
I have tried to offer a historical account of a success story, as I saw it develop from the early times when it interested only a few aficionados to the present times when it has pervaded most of cell biochemistry and physiology. It is of course the story of calcium signaling. It became my topic of work when I was a young postdoctoral fellow at The Johns Hopkins University. I entered it through a side door, that of mitochondria, which had been my area of work during my earlier days in Italy. The 1960s and 1970s were glorious times for mitochondrial calcium signaling, but the golden period was not going to last. As I have discussed below, mitochondrial calcium gradually lost appeal, entering a long period of oblivion. Its fading happened as the general area of calcium signaling was instead experiencing a phase of explosive growth, with landmark discoveries at the molecular and cellular levels. These discoveries established that calcium signaling was one of the most important areas of cell biology. However, mitochondria as calcium partners were not dead; they were only dormant. In the 1990s, they were rescued from their state of neglect to the central position of the regulation of cellular calcium signaling, which they had once rightly occupied. Meanwhile, it had also become clear that calcium is an ambivalent messenger. Hardly anything important occurs in cells without the participation of the calcium message, but calcium must be controlled with absolute precision. This is an imperative necessity, which becomes unfortunately impaired in a number of disease conditions that transform calcium into a messenger of death.
Highlights
The village where I was born is close to the Slovenian border in the Italian province of Friuli
The idea of sending me to a boarding school had to be abandoned, so my private teacher for the first three years of high school was the chaplain of our village church
I had to learn the ABCs of laboratory life, from the preparation of solutions, to pipetting, to the forgotten routine methods of analytical chemistry such as the Kjeldahl determination of nitrogen or the glorious Fiske-Subbarow assay for phosphate
Summary
After a while, Azzone felt that muscle biochemistry, at least in the ways it was pursued in the 1950s, was sort of boring He had cast his eye on the much more fashionable topic of bioenergetics, and we timidly started working on mitochondria, with the idea of studying them in dystrophic muscles. He told me about the various research programs of the department, saying that I could take all the time I needed to choose one He added that the transport of calcium by mitochondria might be a wise choice because, he said, this topic had a great future. A number of other postdoctoral fellows (Zdenek Drahota from Prague, Czech Republic, and Jozef Bielawski from Poznan, Poland) had joined the lab, and our work on mitochondrial calcium transport gathered speed It was a very exciting period, as this process had become a hot topic, with numerous laboratories working on it.
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