The role of mitochondrial NAD(P)-Transhydrogenase in the development of Fatty Liver Disease and aging in mice

• Grant number: 19/20855-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2019
• End date: January 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Aníbal Eugênio Vercesi
• Grantee: Claudia Daniele Carvalho Navarro
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/17728-8 - Mitochondrial function and dysfunction: implications for aging and associated diseases, AP.TEM
• Associated scholarship(s): 23/02270-7 - Linking defects in DNA repair to activation of the inflammatory response via cGAS-STING and defects in mitophagy in mononuclear cells from humans with cognitive decline, BE.EP.PD

Abstract

We will study the role of mitochondrial NAD(P)-transhydrogenase (NNT) activity in the development of Fatty Liver Disease and aging in mice. It will be investigated the role of pyruvate dehydrogenase inhibition in the development of Fatty Liver Disease in NNT deficient mice fed a high fat diet. Additionally, the involvement of NNT activity will be evaluated in the process of mitochondrial permeability transition pore opening and aging-related mitochondrial redox imbalance. Methodological approaches will include: maintenance of a mouse colony including performing genetic control and administration of diets and drugs, evaluation of histological aspects of Fatty Liver Disease, assessment of the bioenergetic and redox balance in isolated mitochondria, blood cell isolation, flow cytometry, and measurements of glycolytic rate and oxygen uptake in adherent cells. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NAVARRO, CLAUDIA D. C.; FRANCISCO, ANNELISE; FIGUEIRA, TIAGO R.; RONCHI, JULIANA A.; OLIVEIRA, HELENA C. F.; VERCESI, ANIBAL E.; CASTILHO, ROGER F.. ichloroacetate reactivates pyruvate-supported peroxide removal by liver mitochondria and prevents NAFLD aggravation in NAD(P)(+) transhydrogenase-null mice consuming a high-fat die. European Journal of Pharmacology, v. 917, FEB 15 2022. (20/05202-4, 19/20855-7, 17/17728-8)

SARTORI, MARINA R.; NAVARRO, CLAUDIA D. C.; CASTILHO, ROGER F.; VERCESI, ANIBAL E.. Aggravation of hepatic lipidosis in red-footed tortoise Chelonoidis carbonaria with age is associated with alterations in liver mitochondria. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY, v. 260, p. 8-pg., 2022-03-12. (17/05487-6, 17/17728-8, 19/20855-7)

SARTORI, MARINA R.; NAVARRO, CLAUDIA D. C.; CASTILHO, ROGER F.; VERCESI, ANIBAL E.. nhanced resistance to Ca2+-induced mitochondrial permeability transition in the long-lived red-footed tortoise Chelonoidis carbonari. Journal of Experimental Biology, v. 225, n. 1, JAN 2022. (17/17728-8, 19/20855-7, 17/05487-6)

RUAS, JULIANA S.; SIQUEIRA-SANTOS, EDILENE S.; NAVARRO, CLAUDIA D. C.; CASTILHO, ROGER F.. A dataset describing glycolytic inhibitors overcoming the underestimation of maximal mitochondrial oxygen consumption rate in oligomycin-treated cells. DATA IN BRIEF, v. 40, p. 11-pg., 2022-02-01. (19/20855-7)