Redox regulation of protein phosphoglycerate mutase 5 (PGAM5) in yeast

• Grant number: 25/13665-8
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Luciana Elena de Souza Fraga Machado
• Grantee: Luciana Elena de Souza Fraga Machado
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 19/02605-3 - Structural and functional characterization of mitochondrial protein phosphatases by redox metabolism and their role in cell biology, AP.JP

Abstract

The histidine-based serine threonine protein phosphatase, PGAM5, is an atypical serine/threonine protein phosphatase unrelated to any other protein in this family. PGAM5 is located in the intermembrane space of mitochondria. Furthermore, this protein forms a dodecamer that is organized as an overlapping filament of several dodecamers. PGAM5 is a mitochondrial protein phosphatase evolutionarily conserved among species from Drosophila melanogaster to Homo sapiens, which is involved in the process of apoptosis. Studies show that PGAM5 dephosphorylates the inhibitory sites of ASK1 (apoptosis signal-regulating kinase 1), leading to its activation and promoting increased survival. Additionally, PGAM5 interacts with SKN-1 (protein skinhead 1) causing resistance during nutritional deprivation. Considering that cytoplasmic protein phosphatases are inhibited by oxidants and that mitochondria are one of the main sources of oxidants, we believe that PGAM5 is also regulated by the redox environment. Therefore, we will analyze the impact of its deletion and oxidative stress in yeast to expand the knowledge about its cellular function. (AU)