Peroxiporins: Redox Signal Mediators In and Between Cells (Oxidative Stress and Disease)

To produce energy, aerobic organisms transform oxygen molecules into water. This reductive mechanism yields toxic radical intermediates, collectively known as reactive oxygen species (ROS). Paradoxically, these physiological processes entail the production of potentially damaging species. Evolution has turned this apparent disadvantage into an opportunity for transmitting information. As a result, redox signaling within the cell is an efficient exquisitely organized process. A key element for its regulation is the physical separation of sources and targets into different cell compartments. Peroxiporins, H₂O₂ transporting proteins spanning biological membranes, distribute the signal from emitters to receptors. Thus, these channels are strategically situated in the thin line between life and death, guaranteeing adequate but safe signaling.

Key Features:

- Provides a brief history of the discovery and characterization of peroxiporins
- Reviews key findings on hydrogen peroxide transport across biological membranes
- Discusses the cartography of redox signaling in crowded cells
- Includes lavish illustrations and comprehensive images to facilitate teaching
- Highlights recent findings, outstanding controversies and open questions

Iria Medraño-Fernandez, PhD - Iria Medraño-Fernandez is currently Chair of Excellence Beatriz Galindo at the Department of Bioengineering of the University Carlos III de Madrid (UC3M) and head of the core facility CleanRooms for Bioengeneering. In 2012 she obtained her PhD in Biochemistry and Molecular Biology at the Universidad Complutense of Madrid. Soon after she moved to Milan, to deepen her expertise in signal transduction mechanisms by focusing on peroxiporin-controlled signaling pathways. Since 2020 she leads the lab ‘Redox signaling in Regenerative Medicine’ inserted in the Tissue Engineering in Regenerative Medicine (TERMEG) UC3M unit. Her main research interest is centered on deciphering how cells maintain redoxtasis to achieve desired outcomes, particularly during skin regeneration, using peroxiporins both as subjects of study and as genetically engineered research tools.

Prof. Gerd Patrick Bienert (born in Rothenburg ob der Tauber, Germany, in 1978) is professor for Crop Physiology at the Technical University of Munich in Germany since 2020. The main research objectives of Prof. Bienert are to understand metalloid- and water efficiency mechanisms in crop plants. Prof. Bienert’s research targets the understanding of the physiology of plants down to the structure and function of genes and proteins as well as relevant mechanisms, which allow optimizing biotechnologically and agriculturally important quality and yield traits and the generation of crops, which are beneficial for the society in terms of food-security and food-safety. A second research focus is on the molecular elucidation of whether and how the transport of hydrogen peroxide through plant and mammalian aquaporins is regulated.

Prof. Bienert studied biology at the Universities of Würzburg and Darmstadt, Germany. Following this, he did his PhD in Molecular Plant Nutrition in Copenhagen, Denmark. Using yeast toxicity growth experiments and direct transport assays, he and colleagues provided first time functional evidence that specific aquaporins facilitate the transport of hydrogen peroxide across membranes: the nowadays called "peroxiporins". A by now, routinely applied assay to characterize the transmembrane transport of hydrogen peroxide had been developed. He then moved on to be a postdoctoral researcher at UCLouvain, Belgium. Between 2013 and 2020, he headed an independent research group at the Leibniz Institute of Plant Genetics and Crop Plant Research in Gatersleben dealing with the elucidations of mechanisms regulating metalloid efficiency in crops. In 2021, Prof. Bienert was Laureate of the Joseph Schepkens award for "Plant Genetics" from the Belgian Royal Academy for Science for his work on "Water and Metalloid Transport in Arable Crops".

During his training as a hematologist at the University of Genoa, Roberto Sitia became fascinated by the immune system, and how our body manages to produce, assemble and release highly specific antibodies against the most diverse substances it encounters. Always in search of mechanistic explanations to the scientific problem at stake, he worked at the Memorial Sloan Kettering Cancer Center in New York (US) and then at the MRC Laboratory of Molecular Biology in Cambridge. In 1990, he was then recruited at the San Raffaele Hospital in Milan to help in the design, management and development of a competitive Research Institute (DiBiT) and a Medical School (UniSR), both of which are now considered the best in Italy. Since over two decades RS is a full professor of Molecular Biology at UniSR.

Key discoveries include the mechanisms of i) protein quality control and traffic jams in the secretory pathway, ii) unconventional (leaderless) protein secretion, iii) oxidative folding; iv) de novo ER biogenesis during the differentiation of antibody producing cells and v) redox adaptation to increased Ig secretion and lifespan control. Recently, his lab pioneered the discovery and characterization of peroxiporins, and their role in inter- and intra-cellular redox signaling and homeostasis. Member elect of the European Molecular Biology Organization, he has published over 170 papers, many of which are highly cited breakthroughs. Many investigators trained in his lab now occupy leading positions all over the world. Besides his scientific and managerial activities, Roberto Sitia fights for the survival and growth of basic sciences, a tough challenge in a period in which obscurantism is getting space.