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

Author(s)

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

• Document type: Journal article
• Source: MOLECULAR METABOLISM; v. 78, p. 11-pg., 2023-10-14.

Abstract

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)

• FAPESP's process: 15/06463-8 - Role of Physical Training in the UPRmt
• Grantee: Rodrigo Stellzer Gaspar
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 19/21709-4 - Implications of mitonuclear imbalance and UPRmt in hypothalamic neurons in the genesis of Obesity
• Grantee: Eduardo Rochete Ropelle
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/13443-1 - Implications of aerobic exercise on the Notch 1 signaling pathway and regulation of lipogenesis and gluconeogenesis in the liver
• Grantee: José Rodrigo Pauli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/11820-5 - Nr1d1 function on the aging-associated Sarcopenia
• Grantee: Adelino Sanchez Ramos da Silva
• Support Opportunities: Research Projects - Thematic Grants