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 Sjøberg, Jørgen F P Wojtaszewski, Jacob F Jeppesen, Bente Kiens, Steven P Gygi, Erik A Richter, Diane Mathis, Edward T Chouchani
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...
October 1, 2020: Cell