pH-gated succinate secretion regulates muscle remodeling in response to exercise

Department of Nutrition, Exercise and Sports

pH-gated succinate secretion regulates muscle remodeling in response to exercise

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

pH-gated succinate secretion regulates muscle remodeling in response to exercise. / Reddy, Anita; Bozi, Luiz H M; Yaghi, Omar K; Mills, Evanna L; Xiao, Haopeng; Nicholson, Hilary E; Paschini, Margherita; Paulo, Joao A; Garrity, Ryan; Laznik-Bogoslavski, Dina; Ferreira, Julio C B; Carl, Christian Strini; Sjøberg, Kim Anker; Wojtaszewski, Jørgen; Jeppesen, Jacob F; Kiens, Bente; Gygi, Steven P; Richter, Erik A.; Mathis, Diane; Chouchani, Edward T.

In: Cell, Vol. 183, No. 1, 2020, p. 62-75, e1-e10.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

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, J, Jeppesen, JF, Kiens, B, Gygi, SP, Richter, EA, Mathis, D & Chouchani, ET 2020, 'pH-gated succinate secretion regulates muscle remodeling in response to exercise', Cell, vol. 183, no. 1, pp. 62-75, e1-e10. https://doi.org/10.1016/j.cell.2020.08.039

APA

Reddy, A., Bozi, L. H. M., Yaghi, O. K., Mills, E. L., Xiao, H., Nicholson, H. E., Paschini, M., Paulo, J. A., Garrity, R., Laznik-Bogoslavski, D., Ferreira, J. C. B., Carl, C. S., Sjøberg, K. A., Wojtaszewski, J., Jeppesen, J. F., Kiens, B., Gygi, S. P., Richter, E. A., Mathis, D., & Chouchani, E. T. (2020). pH-gated succinate secretion regulates muscle remodeling in response to exercise. Cell, 183(1), 62-75, e1-e10. https://doi.org/10.1016/j.cell.2020.08.039

Vancouver

Reddy A, Bozi LHM, Yaghi OK, Mills EL, Xiao H, Nicholson HE et al. pH-gated succinate secretion regulates muscle remodeling in response to exercise. Cell. 2020;183(1):62-75, e1-e10. https://doi.org/10.1016/j.cell.2020.08.039

Author

Reddy, Anita ; Bozi, Luiz H M ; Yaghi, Omar K ; Mills, Evanna L ; Xiao, Haopeng ; Nicholson, Hilary E ; Paschini, Margherita ; Paulo, Joao A ; Garrity, Ryan ; Laznik-Bogoslavski, Dina ; Ferreira, Julio C B ; Carl, Christian Strini ; Sjøberg, Kim Anker ; Wojtaszewski, Jørgen ; Jeppesen, Jacob F ; Kiens, Bente ; Gygi, Steven P ; Richter, Erik A. ; Mathis, Diane ; Chouchani, Edward T. / pH-gated succinate secretion regulates muscle remodeling in response to exercise. In: Cell. 2020 ; Vol. 183, No. 1. pp. 62-75, e1-e10.

Bibtex

@article{c703264e8f1a42cdb073b5252f4c9a4f,

title = "pH-gated succinate secretion regulates muscle remodeling in response to exercise",

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.",

keywords = "Faculty of Science, SUCNR1, Exercise, Innervation, Muscle, Succinate",

author = "Anita Reddy and Bozi, {Luiz H M} and Yaghi, {Omar K} and Mills, {Evanna L} and Haopeng Xiao and Nicholson, {Hilary E} and Margherita Paschini and Paulo, {Joao A} and Ryan Garrity and Dina Laznik-Bogoslavski and Ferreira, {Julio C B} and Carl, {Christian Strini} and Sj{\o}berg, {Kim Anker} and J{\o}rgen Wojtaszewski and Jeppesen, {Jacob F} and Bente Kiens and Gygi, {Steven P} and Richter, {Erik A.} and Diane Mathis and Chouchani, {Edward T}",

year = "2020",

doi = "10.1016/j.cell.2020.08.039",

language = "English",

volume = "183",

pages = "62--75, e1--e10",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "1",

}

RIS

TY - JOUR

T1 - pH-gated succinate secretion regulates muscle remodeling in response to exercise

AU - Reddy, Anita

AU - Bozi, Luiz H M

AU - Yaghi, Omar K

AU - Mills, Evanna L

AU - Xiao, Haopeng

AU - Nicholson, Hilary E

AU - Paschini, Margherita

AU - Paulo, Joao A

AU - Garrity, Ryan

AU - Laznik-Bogoslavski, Dina

AU - Ferreira, Julio C B

AU - Carl, Christian Strini

AU - Sjøberg, Kim Anker

AU - Wojtaszewski, Jørgen

AU - Jeppesen, Jacob F

AU - Kiens, Bente

AU - Gygi, Steven P

AU - Richter, Erik A.

AU - Mathis, Diane

AU - Chouchani, Edward T

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Faculty of Science

KW - SUCNR1

KW - Exercise

KW - Innervation

KW - Muscle

KW - Succinate

U2 - 10.1016/j.cell.2020.08.039

DO - 10.1016/j.cell.2020.08.039

M3 - Journal article

C2 - 32946811

VL - 183

SP - 62-75, e1-e10

JO - Cell

JF - Cell

SN - 0092-8674

IS - 1

ER -

ID: 249064339