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Calcium-regulated changes in mitochondrial phenotype in skeletal muscle cells.
Am J Physiol Cell Physiol. 2004 May; 286(5):C1053-61.AJ

Abstract

Cytochrome c expression and mitochondrial biogenesis can be invoked by elevated intracellular Ca(2+) in muscle cells. To characterize the potential role of Ca(2+) as a messenger involved in mitochondrial biogenesis in muscle, we determined the effects of the Ca(2+) ionophore A-23187 on the expression of nuclear- and mitochondrially encoded genes. Treatment of myotubes with 1 microM A-23187 for 48-96 h increased nuclear-encoded beta-subunit F(1)ATPase and malate dehydrogenase (MDH) mRNA levels by 50-100% (P < 0.05) but decreased mRNA levels of glutamate dehydrogenase (GDH) by 19% (P < 0.05). mRNA levels of the cytochrome c oxidase (COX) nuclear-encoded subunits IV, Vb, and VIc were unchanged, whereas the mitochondrially encoded subunits COX II and COX III were decreased by 30 and 70%, respectively (P < 0.05). This was paralleled by a 20% decrease (P < 0.05) in COX activity. These data suggest that cytoplasmic Ca(2+) differentially regulates the mRNA level of nuclear and mitochondrial genes. The decline in COX II and III mRNA may be mediated by Tfam, because A-23187 modestly reduced Tfam levels by 48 h. A-23187 induced time-dependent increases in Egr-1 mRNA, along with the activation of ERK1/2 and AMP-activated protein kinase. MEK inhibition with PD-98059 attenuated the increase in Egr-1 mRNA. A-23187 also increased Egr-1, serum response factor, and Sp1 protein expression, transcription factors implicated in mitochondrial biogenesis. Egr-1 overexpression increased nuclear-encoded cytochrome c transcriptional activation by 1.5-fold (P < 0.05) and reduced GDH mRNA by 37% (P < 0.05) but had no effect on MDH or beta-subunit F(1)ATPase mRNA. These results indicate that changes in intracellular Ca(2+) can modify mitochondrial phenotype, in part via the involvement of Egr-1.

Authors+Show Affiliations

Dept. of Biology, York University, Toronto, Ontario, M3J 1P3 Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15075204

Citation

Freyssenet, Damien, et al. "Calcium-regulated Changes in Mitochondrial Phenotype in Skeletal Muscle Cells." American Journal of Physiology. Cell Physiology, vol. 286, no. 5, 2004, pp. C1053-61.
Freyssenet D, Irrcher I, Connor MK, et al. Calcium-regulated changes in mitochondrial phenotype in skeletal muscle cells. Am J Physiol, Cell Physiol. 2004;286(5):C1053-61.
Freyssenet, D., Irrcher, I., Connor, M. K., Di Carlo, M., & Hood, D. A. (2004). Calcium-regulated changes in mitochondrial phenotype in skeletal muscle cells. American Journal of Physiology. Cell Physiology, 286(5), C1053-61.
Freyssenet D, et al. Calcium-regulated Changes in Mitochondrial Phenotype in Skeletal Muscle Cells. Am J Physiol, Cell Physiol. 2004;286(5):C1053-61. PubMed PMID: 15075204.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Calcium-regulated changes in mitochondrial phenotype in skeletal muscle cells. AU - Freyssenet,Damien, AU - Irrcher,Isabella, AU - Connor,Michael K, AU - Di Carlo,Martino, AU - Hood,David A, Y1 - 2004/01/07/ PY - 2004/4/13/pubmed PY - 2004/5/21/medline PY - 2004/4/13/entrez SP - C1053 EP - 61 JF - American journal of physiology. Cell physiology JO - Am. J. Physiol., Cell Physiol. VL - 286 IS - 5 N2 - Cytochrome c expression and mitochondrial biogenesis can be invoked by elevated intracellular Ca(2+) in muscle cells. To characterize the potential role of Ca(2+) as a messenger involved in mitochondrial biogenesis in muscle, we determined the effects of the Ca(2+) ionophore A-23187 on the expression of nuclear- and mitochondrially encoded genes. Treatment of myotubes with 1 microM A-23187 for 48-96 h increased nuclear-encoded beta-subunit F(1)ATPase and malate dehydrogenase (MDH) mRNA levels by 50-100% (P < 0.05) but decreased mRNA levels of glutamate dehydrogenase (GDH) by 19% (P < 0.05). mRNA levels of the cytochrome c oxidase (COX) nuclear-encoded subunits IV, Vb, and VIc were unchanged, whereas the mitochondrially encoded subunits COX II and COX III were decreased by 30 and 70%, respectively (P < 0.05). This was paralleled by a 20% decrease (P < 0.05) in COX activity. These data suggest that cytoplasmic Ca(2+) differentially regulates the mRNA level of nuclear and mitochondrial genes. The decline in COX II and III mRNA may be mediated by Tfam, because A-23187 modestly reduced Tfam levels by 48 h. A-23187 induced time-dependent increases in Egr-1 mRNA, along with the activation of ERK1/2 and AMP-activated protein kinase. MEK inhibition with PD-98059 attenuated the increase in Egr-1 mRNA. A-23187 also increased Egr-1, serum response factor, and Sp1 protein expression, transcription factors implicated in mitochondrial biogenesis. Egr-1 overexpression increased nuclear-encoded cytochrome c transcriptional activation by 1.5-fold (P < 0.05) and reduced GDH mRNA by 37% (P < 0.05) but had no effect on MDH or beta-subunit F(1)ATPase mRNA. These results indicate that changes in intracellular Ca(2+) can modify mitochondrial phenotype, in part via the involvement of Egr-1. SN - 0363-6143 UR - https://www.unboundmedicine.com/medline/citation/15075204/Calcium_regulated_changes_in_mitochondrial_phenotype_in_skeletal_muscle_cells_ L2 - http://www.physiology.org/doi/full/10.1152/ajpcell.00418.2003?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -