Evaluation of mitonuclear imbalance and UPRmt in the skeletal muscle of exercise mice: The role JNK and PKR.

• Grant number: 18/07634-9
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2018
• End date: August 31, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Eduardo Rochete Ropelle
• Grantee: Eduardo Rochete Ropelle
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated researchers: Adelino Sanchez Ramos da Silva ; Dennys Esper Corrêa Cintra ; Leandro Pereira de Moura

Abstract

Mitonuclear imbalance and UPRmt (mitochondrial Unfolded Protein Response) are cellular phenomena activated under stress conditions and involving mitochondrial metabolism. These responses are largely related to mitochondrial biogenesis, improved mitochondrial function and cell metabolism, and increased longevity in several organisms. Mitonuclear imbalance is characterized by the alteration of the stoichiometric equilibrium between proteins encoded by mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). This imbalance stimulates mitochondrial biogenesis via the PGC-1/NRF-1/ TFAM pathway. The second (UPRmt), is characterized as a stress-adaptive response that stimulates chaperones (HSPs) and mitochondrial proteases, in order to ensure the integrity and functionality of mitochondria. In this sense, the unleashing of mitonuclear imbalance and UPRmt became an important mechanism for the induction of mitochondrial biogenesis and an improvement in the function of this organelle. Some studies suggest that the activation of mitonuclear imbalance and UPRmt is initiated from stress-sensitive cytoplasmic proteins, especially JNK and PKR. Therefore, we hypothesize that physical exercise can trigger mitral and UPRmt imbalance in the skeletal muscle through the activation of JNK and / or PKR, stimulating mitochondrial biogenesis and improving mitochondrial function. The realization of the current project could open new perspectives in the understanding of the improvement of the oxidative capacity of the skeletal muscles induced by the physical exercise. (AU)

Scientific publications

(7)

(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)

CORDEIRO, ANDRE VICTOR; PERUCA, GUILHERME FRANCISCO; BRAGA, RENATA ROSSETO; BRICOLA, RAFAEL SANTOS; LENHARE, LUCIENE; RODRIGUES SILVA, VAGNER RAMON; ANARUMA, CHADI PELLEGRINI; KATASHIMA, CARLOS KIYOSHI; CRISOL, BARBARA MOREIRA; BARBOSA, LUCAS TORRES; et al. High-intensity exercise training induces mitonuclear imbalance and activates the mitochondrial unfolded protein response in the skeletal muscle of aged mice. GEROSCIENCE, v. 43, n. 3, SI, JUL 2020. (18/07634-9, 11/09656-0)

CORDEIRO, ANDRE V.; SILVA, VAGNER R. R.; PAULI, JOSE R.; DA SILVA, ADELINO S. R.; CINTRA, DENNYS E.; MOURA, LEANDRO P.; ROPELLE, EDUARDO R.. The role of sphingosine-1-phosphate in skeletal muscle: Physiology, mechanisms, and clinical perspectives. Journal of Cellular Physiology, v. 234, n. 7, p. 10047-10059, JUL 2019. (18/07634-9, 11/09656-0)

CORDEIRO, V, ANDRE; BRICOLA, RAFAEL S.; BRAGA, RENATA R.; LENHARE, LUCIENE; SILVA, VAGNER R. R.; ANARUMA, CHADI P.; KATASHIMA, CARLOS K.; CRISOL, BARBARA M.; SIMABUCO, FERNANDO M.; SILVA, ADELINO S. R.; et al. Aerobic Exercise Training Induces the Mitonuclear Imbalance and UPRmt in the Skeletal Muscle of Aged Mice. JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, v. 75, n. 12, p. 2258-2261, DEC 2020. (18/07634-9)

ROPELLE, EDUARDO ROCHETE; RAMOS DA SILVA, ADELINO SANCHEZ; CINTRA, DENNYS ESPER; DE MOURA, LEANDRO PEREIRA; TEIXEIRA, ANA MARIA; PAULI, JOSE RODRIGO. Physical Exercise: A Versatile Anti-Inflammatory Tool Involved in the Control of Hypothalamic Satiety Signaling. EXERCISE IMMUNOLOGY REVIEW, v. 27, p. 17-pg., 2021-01-01. (19/00227-1, 18/20872-6, 18/07634-9)

CORDEIRO, ANDRE VICTOR; PERUCA, GUILHERME FRANCISCO; BRAGA, RENATA ROSSETO; BRICOLA, RAFAEL SANTOS; LENHARE, LUCIENE; RODRIGUES SILVA, VAGNER RAMON; ANARUMA, CHADI PELLEGRINI; KATASHIMA, CARLOS KIYOSHI; CRISOL, BARBARA MOREIRA; BARBOSA, LUCAS TORRES; et al. High-intensity exercise training induces mitonuclear imbalance and activates the mitochondrial unfolded protein response in the skeletal muscle of aged mice. GEROSCIENCE, v. 43, n. 3, p. 6-pg., 2020-07-31. (18/07634-9, 11/09656-0)

CRISOL, BARBARA M.; VEIGA, CAMILLA B.; BRAGA, RENATA R.; LENHARE, LUCIENE; BAPTISTA, IGOR L.; GASPAR, RAFAEL C.; MUNOZ, VITOR R.; CORDEIRO, ANDRE V.; DA SILVA, ADELINO S. R.; CINTRA, DENNYS E.; et al. NAD(+)precursor increases aerobic performance in mice. EUROPEAN JOURNAL OF NUTRITION, v. 59, n. 6, p. 2427-2437, SEP 2020. (16/01089-3, 18/07634-9, 16/05499-1)

BRAGA, RENATA R.; CRISOL, BARBARA M.; BRICOLA, RAFAEL S.; SANT'ANA, MARCELLA R.; NAKANDAKARI, SUSANA C. B. R.; COSTA, SULEYMA O.; PRADA, PATRICIA O.; DA SILVA, ADELINO S. R.; MOURA, LEANDRO P.; PAULI, JOSE R.; et al. Exercise alters the mitochondrial proteostasis and induces the mitonuclear imbalance and UPRmt in the hypothalamus of mice. SCIENTIFIC REPORTS, v. 11, n. 1, FEB 15 2021. (17/18695-6, 13/07607-8, 18/07634-9, 19/21709-4)