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Abstract

The expression of the orphan receptor, Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3), is upregulated in response to exercise, suggesting that it could be influential in altering gene expression for skeletal muscle adaptation to exercise. Recent research has demonstrated that when NR4A3 was knocked down in skeletal muscle cells, there was decreased expression of mitochondrial proteins, including those of the oxidative phosphorylation system (OXPHOS). The effect of deficient NR4A3 expression on mitochondrial proteins in mouse skeletal muscle is unknown. PURPOSE: We tested the hypothesis that NR4A3-knockout (KO) would suppress the expression of mitochondrial proteins in mouse skeletal muscle. METHODS: To test this hypothesis, the gastrocnemius muscles of 10 global NR4A3 knockout and 10 wild-type mice were collected, homogenized, and analyzed using western blotting. The proteins examined included OXPHOS proteins, PGC1, p-ACC, p-raptor, and cytochrome C. RESULTS: Contrary to our hypothesis, there was no significant difference in protein expression between the knockout and wild-type mice for any of the measured proteins. However, a strong trend (p=0.07 - 0.14) for decreased expression of some OXPHOS components was observed in knockout mice. CONCLUSION: Our findings suggest that contrary to findings in cultured muscle, the lack of NR4A3 in vivo does not heavily impact mitochondrial content, although it may affect components of the electron transport chain, and further testing of mitochondrial function would be beneficial. The lack of effect may be related to compensation by NR4A1, a protein related to NR4A3.

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