Skip to main content
. Author manuscript; available in PMC: 2021 Oct 1.
Published in final edited form as: Cell. 2020 Sep 17;183(1):62–75.e17. doi: 10.1016/j.cell.2020.08.039

Figure 4. Succinate-SUCNR1 Signaling Controls Non-cell-autonomous Transcriptional Responses to Acute Exercise.

Figure 4.

(A) Phosphoproteomics analysis of TA muscle immediately following exercise, comparing the relative abundance of phosphorylation of the WT and SUCNR1 KO. Sites exhibiting over 50% elevation in the WT versus SUCNR1 KO are highlighted and were subjected to kinase enrichment analysis. Top enriched pathways and those known to be downstream of SUCNR1 agonism are highlighted. A full list is provided in Table S3 (n = 4).

(B) SUCNR1 is expressed in muscle tissue but not mature myotubes or immortalized C2C12 myoblasts, whereas non-myofibrillar cells resident in muscle tissue express SUCNR1 (n = 3–4).

(C) TA muscle RNAScope ISH to establish cellular localization of SUCNR1. Red, SUCNR1; pdgfrα stromal cell marker; yellow, desmin myofiber marker. SUCNR1 exhibits strong colocalization with PDGFRα and anti-localization with desmin. Three representative fields of view are shown.

(D) Manders’ colocalization coefficient of TA muscle RNAScope ISH data from (C). Coefficients of less than 0.1 are considered completely anti-colocalized, which is validated by the anti-colocalization control of pdgfrα and desmin (distinct cell type markers). SUCNR1 is completely anti-colocalized with desmin (myofibers) and colocalizes with pdgfrα (stromal cells) (n = 3).

(E) A model of non-cell-autonomous regulation of muscle remodeling post-exercise via SUCNR1.

(F) The SUCNR1-dependent transcriptional landscape post exercise in muscle satellite cells (CD45−, CD31−, Sca1−, Vcam). Example significant pathways show decreased expression in SUCNR1 KO (highlighted). See Table S4 for a full list.

(G) The SUCNR1-dependent transcriptional landscape after exercise in stromal cells (CD45−, CD31−, Sca1+, PDGFRa+). Example significant pathways show decreased expression in SUCNR1 KO (highlighted). See Table S4 for a full list.

(H) The SUCNR1-dependent transcriptional landscape after exercise in muscle hematopoietic cells (CD45). Example significant pathways show decreased expression in SUCNR1 KO (highlighted). See Table S4 for a full list.

(I) The SUCNR1-dependent transcriptional landscape after exercise in endothelial cells (CD45−, CD31+). Example significant pathways show decreased expression in SUCNR1 KO (highlighted). See Table S4 for a full list.

Data are represented as mean ± SEM.