pH-Gated Succinate Secretion Regulates Muscle Remodeling in Response to Exercise.
pH-Gated Succinate Secretion Regulates Muscle Remodeling in Response to Exercise.
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DOI：
10.1016/j.cell.2020.08.039
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发表时间：
2020-10-01
期刊：
影响因子：
64.5
通讯作者：
Chouchani ET
中科院分区：
文献类型：
--
作者：
Reddy A;Bozi LHM;Yaghi OK;Mills EL;Xiao H;Nicholson HE;Paschini M;Paulo JA;Garrity R;Laznik-Bogoslavski D;Ferreira JCB;Carl CS;Sjøberg KA;Wojtaszewski JFP;Jeppesen JF;Kiens B;Gygi SP;Richter EA;Mathis D;Chouchani ET
为了响应运动过程中骨骼肌的收缩，旁分泌因子协调组织重塑，这是这种健康适应的基础。在这里，我们描述了一个pH传感代谢物信号，通过运动启动肌肉重塑。在小鼠和人类中，运动骨骼肌将线粒体代谢物琥珀酸释放到局部的线粒体和循环中。琥珀酸的选择性分泌是由其瞬时质子化促进的，这发生在肌肉细胞酸化时。在质子化的单羧酸形式中，琥珀酸被赋予单羧酸转运蛋白1的转运底物，其促进pH门控释放。分泌后，琥珀酸通过其同源受体SUCNR1在肌肉组织中的非肌原纤维细胞中发出信号，以控制肌肉重塑转录程序。这种琥珀酸SUCNR1信号传导是响应运动训练的肌肉神经支配、肌肉基质重塑和肌肉力量的旁分泌调节所必需的。总之，我们定义了一个生物能量传感器在肌肉中，利用细胞内的pH值和琥珀酸来协调组织适应运动。Reddy等人确定了一种生物能量传感器，其使用pH和琥珀酸盐来调节肌肉组织对运动的适应。
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 through 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. Reddy et al. identify a bioenergetic sensor that uses pH and succinate to regulate muscle tissue adaptation to exercise.
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影响因子：
4.6
作者：
Campos JC;Baehr LM;Gomes KMS;Bechara LRG;Voltarelli VA;Bozi LHM;Ribeiro MAC;Ferreira ND;Moreira JBN;Brum PC;Bodine SC;Ferreira JCB
通讯作者：
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作者：
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5.5
作者：
BULLER, AJ;ECCLES, JC;ECCLES, RM
通讯作者：
ECCLES, RM
影响因子：
3.4
作者：
Eng, Jimmy K.;Jahan, Tahmina A.;Hoopmann, Michael R.
通讯作者：
Hoopmann, Michael R.