Physical exercise elicits UPRmt in the skeletal muscle: The role of c-Jun N-terminal kinase

Autor(es)

Gaspar, Rodrigo Stellzer ; Katashima, Carlos Kiyoshi ; Crisol, Barbara Moreira ; Carneiro, Fernanda Silva ; Sampaio, Igor ; dos Reis Silveira, Leonardo ; da Silva, Adelino Sanchez Ramos ; Cintra, Dennys Esper ; Pauli, Jose Rodrigo ; Ropelle, Eduardo Rochete

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR METABOLISM; v. 78, p. 11-pg., 2023-10-14.

Resumo

Objective: The mitochondrial unfolded protein response (UPRmt) is an adaptive cellular response to stress to ensure mitochondrial proteostasis and function. Here we explore the capacity of physical exercise to induce UPRmt in the skeletal muscle. Methods: Therefore, we combined mouse models of exercise (swimming and treadmill running), pharmacological intervention, and bioinfor-matics analyses. Results: Firstly, RNA sequencing and Western blotting analysis revealed that an acute aerobic session stimulated several mitostress-related genes and protein content in muscle, including the UPRmt markers. Conversely, using a large panel of isogenic strains of BXD mice, we identified that BXD73a and 73b strains displayed low levels of several UPRmt-related genes in the skeletal muscle, and this genotypic feature was accompanied by body weight gain, lower locomotor activity, and aerobic capacity. Finally, we identified that c-Jun N-terminal kinase (JNK) activation was critical in exercise-induced UPRmt in the skeletal muscle since pharmacological JNK pathway inhibition blunted exercise-induced UPRmt markers in mice muscle. Conclusion: Our findings provide new insights into how exercise triggers mitostress signals toward the oxidative capacity in the skeletal muscle. (c) 2023 The Author(s). Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). (AU)

• Processo FAPESP: 15/06463-8 - Papel do Treinamento Físico na UPRmt da musculatura esquelética de camundongos
• Beneficiário: Rodrigo Stellzer Gaspar
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 19/21709-4 - Implicações do desequilíbrio mitonuclear e da UPRmt em neurônios hipotalâmicos na gênese da Obesidade
• Beneficiário: Eduardo Rochete Ropelle
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 20/13443-1 - Implicações do exercício físico aeróbio sobre a via de sinalização da Notch 1 e regulação da lipogênese e gliconeogênese no fígado
• Beneficiário: José Rodrigo Pauli
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/11820-5 - Função do Nr1d1 sobre a Sarcopenia associada ao envelhecimento
• Beneficiário: Adelino Sanchez Ramos da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Temático