代謝分子琥珀酸可調節肌肉重塑
作者：
小柯機器人發布時間：2020/9/18 15:04:12
美國丹娜-法伯癌症研究所Edward T. Chouchani小組發現，pH門控的琥珀酸分泌調節運動對肌肉的重塑。該項研究成果於2020年9月17日在線發表在《細胞》雜誌上。
研究人員報導了一種pH敏感的代謝物信號，其會在運動時引發肌肉重塑。在小鼠和人類中，鍛鍊骨骼肌會將線粒體代謝物琥珀酸釋放到局部間質和循環中。琥珀酸的選擇性分泌通過其瞬時質子化而促進，這在肌肉細胞酸化時發生。質子化一元羧酸形式的琥珀酸成為單羧酸鹽轉運蛋白1的轉運底物，可促進pH門控釋放。分泌後，琥珀酸通過其同源受體SUCNR1在肌肉組織的非肌原纖維細胞中發出信號，從而控制肌肉重塑的轉錄程序。琥珀酸-SUCNR1信號是旁神經調節肌肉神經支配、調節肌肉基質重塑以及響應運動訓練的肌肉力量所必需的。
總而言之，研究人員在肌肉中定義了一種生物能傳感器，其利用細胞內pH和琥珀酸來協調組織對運動的適應。
據悉，為響應運動過程中的骨骼肌收縮，旁分泌因子會協調組織重塑，是健康性適應的基礎。
附：英文原文
Title: pH-Gated Succinate Secretion Regulates Muscle Remodeling in Response to Exercise
Author: Anita Reddy, Luiz H.M. Bozi, Omar K. Yaghi, Evanna L. Mills, Haopeng Xiao, Hilary E. Nicholson, Margherita Paschini, Joao A. Paulo, Ryan Garrity, Dina Laznik-Bogoslavski, Julio C.B. Ferreira, Christian S. Carl, Kim A. Sjberg, Jrgen F.P. Wojtaszewski, Jacob F. Jeppesen, Bente Kiens, Steven P. Gygi, Erik A. Richter, Diane Mathis, Edward T. Chouchani
Issue&Volume: 2020-09-17
Abstract: In response to skeletal muscle contraction during exercise, paracrine factors coordinatetissue remodeling, which underlies this healthy adaptation. Here we describe a pH-sensingmetabolite signal that initiates muscle remodeling upon exercise. In mice and humans,exercising skeletal muscle releases the mitochondrial metabolite succinate into thelocal interstitium and circulation. Selective secretion of succinate is facilitatedby its transient protonation, which occurs upon muscle cell acidification. In theprotonated monocarboxylic form, succinate is rendered a transport substrate for monocarboxylatetransporter 1, which facilitates pH-gated release. Upon secretion, succinate signalsvia its cognate receptor SUCNR1 in non-myofibrillar cells in muscle tissue to controlmuscle-remodeling transcriptional programs. This succinate-SUCNR1 signaling is requiredfor paracrine regulation of muscle innervation, muscle matrix remodeling, and musclestrength in response to exercise training. In sum, we define a bioenergetic sensorin muscle that utilizes intracellular pH and succinate to coordinate tissue adaptationto exercise.
DOI: 10.1016/j.cell.2020.08.039
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31081-3
Cell：《細胞》，創刊於1974年。隸屬於細胞出版社，最新IF：36.216