pH-Gated Succinate Secretion Regulates Muscle Remodeling in Response to Exercise.
Cell
; 183(1): 62-75.e17, 2020 10 01.
Article
em En
| MEDLINE
| ID: mdl-32946811
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 mitochondrial 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Músculo Esquelético
/
Ácido Succínico
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Receptores Acoplados a Proteínas G
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos