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Cardiolipin Synthesis in Skeletal Muscle Is Rhythmic and Modifiable by Age and Diet.
Oxid Med Cell Longev. 2020; 2020:5304768.OM

Abstract

Circadian clocks regulate metabolic processes in a tissue-specific manner, which deteriorates during aging. Skeletal muscle is the largest metabolic organ in our body, and our previous studies highlight a key role of circadian regulation of skeletal muscle mitochondria in healthy aging. However, a possible circadian regulation of cardiolipin (CL), the signature lipid class in the mitochondrial inner membrane, remains largely unclear. Here, we show that CL levels oscillate during the diurnal cycle in C2C12 myotubes. Disruption of the Ror genes, encoding the ROR nuclear receptors in the secondary loop of the circadian oscillator, in C2C12 cells was found to dampen core circadian gene expression. Importantly, several genes involved in CL synthesis, including Taz and Ptpmt1, displayed rhythmic expression which was disrupted or diminished in Ror-deficient C2C12 cells. In vivo studies using skeletal muscle tissues collected from young and aged mice showed diverse effects of the clock and aging on the oscillatory expression of CL genes, and CL levels in skeletal muscle were enhanced in aged mice relative to young mice. Finally, consistent with a regulatory role of RORs, Nobiletin, a natural agonist of RORs, was found to partially restore transcripts levels of CL synthesis genes in aged muscle under a dietary challenge condition. Together, these observations highlight a rhythmic CL synthesis in skeletal muscle that is dependent on RORs and modifiable by age and diet.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX 77030, USA.Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX 77030, USA.Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX 77030, USA.Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX 77030, USA.Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX 77030, USA.Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX 77030, USA.Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX 77030, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32617138

Citation

Nohara, Kazunari, et al. "Cardiolipin Synthesis in Skeletal Muscle Is Rhythmic and Modifiable By Age and Diet." Oxidative Medicine and Cellular Longevity, vol. 2020, 2020, p. 5304768.
Nohara K, Kim E, Wirianto M, et al. Cardiolipin Synthesis in Skeletal Muscle Is Rhythmic and Modifiable by Age and Diet. Oxid Med Cell Longev. 2020;2020:5304768.
Nohara, K., Kim, E., Wirianto, M., Mileykovskaya, E., Dowhan, W., Chen, Z., & Yoo, S. H. (2020). Cardiolipin Synthesis in Skeletal Muscle Is Rhythmic and Modifiable by Age and Diet. Oxidative Medicine and Cellular Longevity, 2020, 5304768. https://doi.org/10.1155/2020/5304768
Nohara K, et al. Cardiolipin Synthesis in Skeletal Muscle Is Rhythmic and Modifiable By Age and Diet. Oxid Med Cell Longev. 2020;2020:5304768. PubMed PMID: 32617138.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiolipin Synthesis in Skeletal Muscle Is Rhythmic and Modifiable by Age and Diet. AU - Nohara,Kazunari, AU - Kim,Eunju, AU - Wirianto,Marvin, AU - Mileykovskaya,Eugenia, AU - Dowhan,William, AU - Chen,Zheng, AU - Yoo,Seung-Hee, Y1 - 2020/06/14/ PY - 2020/04/05/received PY - 2020/05/13/revised PY - 2020/05/18/accepted PY - 2020/7/4/entrez PY - 2020/7/4/pubmed PY - 2020/7/4/medline SP - 5304768 EP - 5304768 JF - Oxidative medicine and cellular longevity JO - Oxid Med Cell Longev VL - 2020 N2 - Circadian clocks regulate metabolic processes in a tissue-specific manner, which deteriorates during aging. Skeletal muscle is the largest metabolic organ in our body, and our previous studies highlight a key role of circadian regulation of skeletal muscle mitochondria in healthy aging. However, a possible circadian regulation of cardiolipin (CL), the signature lipid class in the mitochondrial inner membrane, remains largely unclear. Here, we show that CL levels oscillate during the diurnal cycle in C2C12 myotubes. Disruption of the Ror genes, encoding the ROR nuclear receptors in the secondary loop of the circadian oscillator, in C2C12 cells was found to dampen core circadian gene expression. Importantly, several genes involved in CL synthesis, including Taz and Ptpmt1, displayed rhythmic expression which was disrupted or diminished in Ror-deficient C2C12 cells. In vivo studies using skeletal muscle tissues collected from young and aged mice showed diverse effects of the clock and aging on the oscillatory expression of CL genes, and CL levels in skeletal muscle were enhanced in aged mice relative to young mice. Finally, consistent with a regulatory role of RORs, Nobiletin, a natural agonist of RORs, was found to partially restore transcripts levels of CL synthesis genes in aged muscle under a dietary challenge condition. Together, these observations highlight a rhythmic CL synthesis in skeletal muscle that is dependent on RORs and modifiable by age and diet. SN - 1942-0994 UR - https://www.unboundmedicine.com/medline/citation/32617138/Cardiolipin_Synthesis_in_Skeletal_Muscle_Is_Rhythmic_and_Modifiable_by_Age_and_Diet L2 - https://doi.org/10.1155/2020/5304768 DB - PRIME DP - Unbound Medicine ER -
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