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Updated: May 4, 2026

Bioenergetic Profile Experiment using C2C12 Myoblast Cells
Published on: December 6, 2010
SOCS2 inhibited mitochondria biogenesis via inhibiting p38 MAPK/ATF2 pathway in C2C12 cells
Lu Gan1, Zhenjiang Liu, Zhenzhen Zhang
1College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, China.
Abstract:
In order to investigate the mechanism of suppressor of cytokine signaling 2 (SOCS2) on mitochondrial biogenesis, RNA interference and over-expression plasmid vectors of SOCS2 were used to transfect murine skeletal muscle C2C12 cells. Results demonstrated that over-expression of SOCS2 inhibited the differentiation of C2C12 cells, and reduced the expression of MyHC, MyoD and MyoG while elevated the protein expression of MSTN. Meanwhile the expression of PGC-1α, MDH, CPT-1 were significantly elevated in the RNA interference of SOCS2 group which were decreased in SOCS2 overexpression group. However, there was no change on the expression of UCP1 in both two groups. JC-1 dyeing showed overexpression of SOCS2 decreased the mitochondrial membrane potential and results of immunofluorescence, real-time PCR and western blotting indicated the increase expression of Cyt c, while interference SOCS2 had the opposite effects in C2C12 cells. Moreover, interference of SOCS2 elevated the p38 phosphorylation level then further increased the phosphorylation of ATF2, whereas overexpression of SOCS2 alleviated this phenomenon. Taken together, our observations indicated that SOCS2 could suppress myotube formation, act as an anti-regulator of mitochondria biogenesis via inhibiting p38 MAPK signal pathway.
Insights
Suppressor of cytokine signaling 2 (SOCS2) inhibits myotube formation and mitochondrial biogenesis by suppressing the p38 MAPK pathway. SOCS2 overexpression reduced mitochondrial potential and cytochrome c, while interference had opposite effects.
Area of Science:
- Cell Biology
- Molecular Biology
- Muscle Physiology
Background:
- Mitochondrial biogenesis is crucial for cellular energy production and muscle function.
- The role of Suppressor of Cytokine Signaling 2 (SOCS2) in regulating mitochondrial biogenesis and muscle differentiation requires further elucidation.
Purpose of the Study:
- To investigate the mechanism by which SOCS2 influences mitochondrial biogenesis and myogenesis in C2C12 cells.
- To determine the effect of SOCS2 on key markers of muscle differentiation and mitochondrial function.
Main Methods:
- Transfection of C2C12 cells with SOCS2 over-expression and RNA interference vectors.
- Analysis of muscle differentiation markers (MyHC, MyoD, MyoG), MSTN, and mitochondrial biogenesis regulators (PGC-1α, MDH, CPT-1, UCP1).
- Assessment of mitochondrial membrane potential (JC-1 dyeing), cytochrome c expression, and p38 MAPK/ATF2 phosphorylation.
Main Results:
- SOCS2 over-expression inhibited C2C12 cell differentiation and reduced MyHC, MyoD, and MyoG expression, while increasing MSTN.
- RNA interference of SOCS2 elevated PGC-1α, MDH, and CPT-1 expression, whereas SOCS2 over-expression decreased them. UCP1 expression remained unchanged.
- SOCS2 over-expression decreased mitochondrial membrane potential and increased cytochrome c, while SOCS2 interference showed opposite effects. SOCS2 modulated p38 MAPK and ATF2 phosphorylation.
Conclusions:
- SOCS2 suppresses myotube formation and acts as an anti-regulator of mitochondrial biogenesis.
- The inhibitory effect of SOCS2 on mitochondrial biogenesis is mediated through the p38 MAPK signaling pathway.
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