Caloric restriction in cardiac ischemia and reperfusion: the role of mitochondrial calcium transporters

• Grant number: 24/07592-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: February 01, 2025
• End date: February 29, 2028
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Alicia Juliana Kowaltowski
• Grantee: Maiara Ingrid Cavalcante Queiroz
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Ischemic heart disease is a major cause of morbidity and mortality worldwide. Cardiac protection strategies have highlighted an important role for mitochondrial activities in cardioprotective intervention. Mitochondrial Ca2+ overload leading to loss of oxidative phosphorylation capacity during ischemia is one of the causal mechanisms of the deleterious effects of infarction, and can be prevented by the action of the Ca2+/Na+ exchanger (NCLX), responsible for removing excess calcium from the mitochondrial matrix. Another intervention that protects hearts in ischemia is the prevention of obesity through caloric restriction. The central hypothesis of this project, based on our preliminary experiments, is that NCLX plays a crucial role in ischemic cardioprotection induced by caloric restriction. We aim to mechanistically understand the protective effect generated by caloric restriction and the possible involvement of the NCLX exchanger in this process, using a combination of cellular and animal models.