小柯机器人

美国丹娜-法伯癌症研究所Edward T. Chouchani小组发现，pH门控的琥珀酸分泌调节运动对肌肉的重塑。该项研究成果于2020年9月17日在线发表在《细胞》杂志上。

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