IRON REGULATORY PROTEIN 1 (IRP1) ACTIVATION AND FERRITIN IRON RELEASE BY ENZYMATICALLY GENERATED TRIPLET CARBONYLS

• Grant number: 25/25849-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: February 20, 2026
• End date: February 19, 2027
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Etelvino José Henriques Bechara
• Grantee: Thiago da Mata Viola Gomes
• Supervisor: Kostas Pantopoulos
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Lady Davis Institute For Medical Research, Canada
• Associated to the scholarship: 22/03864-5 - Quenching of carbonyl metabolites in triplet state by alkylated sorbates, esterified or peptide derivatives, BP.DD

Abstract

Triplet-state carbonyl metabolites generated in vivo can initiate and propagate typical photochemical reactions in the absence of light, leading to loss or gain of cellular functions. This is the case of cyclobutane pyrimidine dimers (CPDs), recently reported to be produced in melanocytes hours after UV irradiation. Electronic excitation of DNA bases was achieved after energy transfer from triplet melanin products formed by reaction with peroxynitrite. Iron regulatory protein 1 (IRP1) and ferritin are key proteins in iron homeostasis. The first one controls ferritin and transferrin receptor synthesis through post-transcriptional modifications, whereas ferritin is responsible for iron storage. Both proteins activity is influenced by reactive oxygens species (ROS). IRP1 is activated by NO* and H2O2, as well as by ¿-aminolaevulinic acid (ALA), the heme group precursor, through O2*- and ALA* generation. Iron release from ferritin can be induced by ALA, methylglyoxal (MG) and aminoacetone (AA), three important reactive carbonyl species (RCS). Due to their n¿¿* transition, triplet carbonyls can behave as diradicals. Our project aims to investigate the interaction between triplet carbonyls and the two key iron metabolism proteins, IRP1 and ferritin. The work will integrate the extensive expertise of Professor Kostas Pantopoulos' research group in iron metabolism with the well-established knowledge on biological chemiexcitation developed by the FAPESP fellow in the home country. (AU)