In Memoriam: Tullio Pozzan (1949 - 2022)#

Tullio Pozzan MAE, widely regarded as the ‘King of Calcium Signaling’, passed away on Saturday 15th October after a relatively short but serious illness. He was internationally recognised as one of the most eminent biologists of his generation. He was elected into numerous academies, including Academia Europaea (1998), the Academia dei Lincei (2001), the US National Academy of Sciences (2006) and the Royal Society (2018).

Tullio Pozzan
Tullio Pozzan at the Royal Society admissions day in London, July 2018. Photo courtesy of The Royal Society

Tullio was born in Venice on 22nd February 1949 into a medical family. He studied Medicine at the University of Padua and received his Doctor of Medicine degree in 1973. For most of his subsequent professional life he worked at the University of Padua, becoming a full Professor of General Pathology in 1986. He was a Long Term EMBO Fellow at the University of Cambridge, 1978 – 1981.

During his Cambridge period, he was part of the trio (with Roger Y Tsien [Nobel Prize in Chemistry 2008] and Tim Rink) who developed a revolutionary technique for the measurements of calcium and hydrogen ions in living cells with intracellular trappable fluorescent calcium ion indicators. This was published in 3 highly cited landmark papers in Nature and J Cell Biol in 1982. The new technique had an enormous influence on the large calcium signaling field and rapidly became (and still remains) THE standard technique for assessing changes in the intracellular calcium ion concentration, a key parameter in the control of virtually all cell activities.

Tullio’s most important work was carried out in Padua in close collaboration with his younger co-worker Rosario Rizzuto MAE. They developed the first genetically encoded probes for calcium ion measurements in selective subcellular localizations (Nature 1992). Using this new technique, their landmark paper published in Science in 1993 (“Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria”) initiated a revolution in our understanding of the role of the mitochondria in cellular calcium ion homeostasis. It also solved a key problem in cellular biology, namely how increased cell activity – elicited by cellular calcium ion signals – is linked to the required increase in mitochondrial energy production. The 1993 Science paper started a new era of cellular signaling work, with a major focus on subcellular micro-domains, which continues to be a crucially important theme in contemporary cellular signaling studies. In 1998, a further Science paper (“Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses”), which has been cited more than 2000 times in the scientific literature, provided very impressive high-resolution evidence for the linkage between local calcium ion signal generation by the endoplasmic reticulum and uptake of calcium ions into the mitochondria. This mitochondrial calcium ion uptake is needed to stimulate the Krebs cycle, thereby generating the ATP that powers cellular activity.

Tullio continued his whole life to generate important tools for cellular biologists and physiologists, turning his interest also to another critical intracellular messenger molecule, namely cyclic adenosine monophosphate. He generated the first genetically encoded fluorescent probe for this messenger and established the concept of cyclic adenosine monophosphate microdomains (Science 2002).

Tullio continued to be very active scientifically, also after his official retirement in 2019, which was celebrated by a magnificent symposium (see picture) in the historic Aula Magna in Palazzo Bo at the University of Padua, where once Galileo had lectured. Last year, he published an important paper in Function describing a new transgenic mouse line for imaging mitochondrial calcium signals. In the accompanying Perspective article, Anant Parekh MAE FRS wrote: “The erudite, innovative, and timely advance take us to the next level, the ability to study mitochondrial Ca2+ signaling in vivo. This landmark contribution will no doubt lead to new vistas in Ca2+ signaling in health and disease.”

Tullio had wonderful support from his wife Carla Scaroni, who cared for him during his final severe illness.

Tullio Pozzan
Tullio Pozzan (number 5 from left, front row) between (left) Rosario Rizzuto (at that time President Vice-Chancellor of the University of Padua) and (right) Tim Rink, at the 2019 symposium in Padua, celebrating Tullio’s 70th birthday.

Ole Petersen CBE MAE FRS, Vice-President of Academia Europaea, said:

“For more than 40 years, I had the enormous privilege of interacting with Tullio at numerous symposia and conferences across the globe. His innovative work was an inspiration for me, as it was for the whole calcium signaling field. Tullio was not only an astoundingly brilliant and rigorous scientist, but also a truly kind and generous friend. In spite of his superior intellect and enormous scientific success, he was devoid of arrogance and, unlike so many other top scientists, willing to serve the scientific community in numerous ways. It was a happy experience for me to have served together with Tullio on the European Editorial Committee of Physiological Reviews as well as on an ERC panel. In the last few years his support as one of the Executive Editors of the American Physiological Society’s new journal Function was vitally important. Tullio leaves a huge legacy. His work was foundational and will remain a cornerstone of cellular physiology, biochemistry and cell biology.”

Rosario Rizzuto MAE said:

“It was a great privilege to have Tullio as mentor at the beginning of my career and then as colleague and dear friend for a scientific lifetime. While so many scientists appreciated and now remember his scientific achievements and his passionate and thoughtful discussions, as a long-time collaborator I would like to highlight the sides of his temperament that made him such a great scientist and inspiring colleague. Tullio was brave, always tackling unresolved, difficult issues, and not adding safe, incremental knowledge to established pictures; Tullio was open to discussion, sharing and questioning ideas and new data with peers as much as with the youngest scientists; Tullio was rigorous, thoroughly testing and doubting the results till any alternative explanation had been unquestionably ruled out. With this scientific imprinting, it is no surprise that Tullio’s trainees will be his legacy in many prestigious international institutions.”

Tullio Pozzan
Tullio Pozzan presents the regulation of mitochondrial function at Academia Europaea celebration of its 30th Anniversary at the Royal Society in September 2018. (Photo courtesy of the Royal Society.)

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