Braga 2021 Sci Rep

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Braga RR, Crisol BM, Brícola RS, Sant'ana MR, Nakandakari SCBR, Costa SO, Prada PO, da Silva ASR, Moura LP, Pauli JR, Cintra DE, Ropelle ER (2021) Exercise alters the mitochondrial proteostasis and induces the mitonuclear imbalance and UPRmt in the hypothalamus of mice. Sci Rep 11:3813.

» PMID: 33589652 Open Access

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, Cintra Dennys E, Ropelle Eduardo R (2021) Sci Rep

Abstract: The maintenance of mitochondrial activity in hypothalamic neurons is determinant to the control of energy homeostasis in mammals. Disturbs in the mitochondrial proteostasis can trigger the mitonuclear imbalance and mitochondrial unfolded protein response (UPRmt) to guarantee the mitochondrial integrity and function. However, the role of mitonuclear imbalance and UPRmt in hypothalamic cells are unclear. Combining the transcriptomic analyses from BXD mice database and in vivo experiments, we demonstrated that physical training alters the mitochondrial proteostasis in the hypothalamus of C57BL/6J mice. This physical training elicited the mitonuclear protein imbalance, increasing the mtCO-1/Atp5a ratio, which was accompanied by high levels of UPRmt markers in the hypothalamus. Also, physical training increased the maximum mitochondrial respiratory capacity in the brain. Interestingly, the transcriptomic analysis across several strains of the isogenic BXD mice revealed that hypothalamic mitochondrial DNA-encoded genes were negatively correlated with body weight and several genes related to the orexigenic response. As expected, physical training reduced body weight and food intake. Interestingly, we found an abundance of mt-CO1, a mitochondrial DNA-encoded protein, in NPY-producing neurons in the lateral hypothalamus nucleus of exercised mice. Collectively, our data demonstrated that physical training altered the mitochondrial proteostasis and induced the mitonuclear protein imbalance and UPRmt in hypothalamic cells.


Bioblast editor: Plangger M


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style 


Organism: Mouse  Tissue;cell: Nervous system  Preparation: Isolated mitochondria 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, NS  HRR: Oxygraph-2k 

2021-02