Characterization of the Expression and Activity of Mitochondrial NAD(P)+ Transhydrogenase (NNT) in Brown Adipose Tissue of Mice

• Grant number: 25/12046-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: June 30, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Roger Frigério Castilho
• Grantee: Rafaela Quirino dos Santos Velasco
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 23/00229-0 - Pathophysiological roles of mitochondrial NAD(P)+ transhydrogenase, AP.TEM

Abstract

The mitochondrial NAD(P)+ transhydrogenase (NNT) catalyzes the transfer of a hydride between NADH and NADP+ coupled to the entry of a proton from the intermembrane space into the mitochondrial matrix. The NADPH generated by NNT activity provides reducing power to peroxide detoxification systems and to anabolic reactions. In recent years, brown adipose tissue (BAT) has attracted increasing interest due to its role in energy metabolism regulation and thermoregulation. Unlike White adipose tissue, which stores energy as triglycerides, BAT dissipates energy as heat through thermogenesis, mediated by brown adipocyte mitochondria that express uncoupling protein 1 (UCP1). The present project aims to characterize the expression and activity of NNT in BAT mitochondria. Comparative studies will be conducted using tissues obtained from C57BL/6 mice that carry a spontaneous mutation in the Nnt gene (C57Unib.B6-Nnt-/-), resulting in the absence of protein expression, and from congenic control mice that express this protein (C57Unib.B6-Nnt+/+). Pre-adipocytes in culture with differentiation properties into brown adipocytes (9B cells) will also be used.