| Full text | |
| Author(s): Show less - |
Reddy, Anita
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Bozi, Luiz H. M.
;
Yaghi, Omar K.
;
Mills, Evanna L.
;
Xiao, Haopeng
;
Nicholson, Hilary E.
;
Paschini, Margherita
;
Paulo, Joao A.
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Garrity, Ryan
;
Laznik-Bogoslavski, Dina
;
Ferreira, Julio C. B.
;
Carl, Christian S.
;
Sjoberg, Kim A.
;
Wojtaszewski, Jorgen F. P.
;
Jeppesen, Jacob F.
;
Kiens, Bente
;
Gygi, Steven P.
;
Richter, Erik A.
;
Mathis, Diane
;
Chouchani, Edward T.
Total Authors: 20
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| Document type: | Journal article |
| Source: | Cell; v. 183, n. 1, p. 31-pg., 2020-10-01. |
| Abstract | |
In response to skeletal muscle contraction during exercise, paracrine factors coordinate tissue remodeling, which underlies this healthy adaptation. Here we describe a pH-sensing metabolite signal that initiates muscle remodeling upon exercise. In mice and humans, exercising skeletal muscle releases the mitochondria! metabolite succinate into the local interstitium and circulation. Selective secretion of succinate is facilitated by its transient protonation, which occurs upon muscle cell acidification. In the protonated monocarboxylic form, succinate is rendered a transport substrate for monocarboxylate transporter 1, which facilitates pH gated release. Upon secretion, succinate signals via its cognate receptor SUCNR1 in non-myofibrillar cells in muscle tissue to control muscle-remodeling transcriptional programs. This succinate-SUCNR1 signaling is required for paracrine regulation of muscle innervation, muscle matrix remodeling, and muscle strength in response to exercise training. In sum, we define a bioenergetic sensor in muscle that utilizes intracellular pH and succinate to coordinate tissue adaptation to exercise. (AU) | |
| FAPESP's process: | 19/07221-9 - Role of mitochondrial unfolded protein response (UPRmt) in doxorubicin-induced cardiomyopathy: applying comparative metabolomics to identify metabolic signatures |
| Grantee: | Luiz Henrique Marchesi Bozi |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |