Redox control of protein disulfide isomerase translocation to caveolae

• Grant number: 24/17892-6
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: March 25, 2025
• End date: May 14, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Francisco Rafael Martins Laurindo
• Grantee: Mayra Cristina de Souza Alves
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Our group has investigated in-depth the highly conserved interaction between the redox chaperone Protein Disulfide Isomerase A1 (PDIA1) and the glycolytic enzyme alpha-enolase (ENO1). ENO1 also acts as a non-canonical plaminogen receptor and mediates its conversion to plasmin, a serinoprotease relevant to cell remodeling. Our hypothesis is that PDIA1 modulates plasmin activation via thiol redox mechanisms involving its interaction with ENO1. Our data indicate that PDIA1-ENO1 interaction occurs in caveolae. Our goal is to locally modulate hydrogen peroxide in caveolae using a DAAO (D-aminoacid oxidase) construct and to monitor the rates of conversion of plasminogen to plasmin in distinct redox conditions.