Calcium-regulated changes in mitochondrial phenotype in skeletal muscle cells
- 1 May 2004
- journal article
- Published by American Physiological Society in American Journal of Physiology-Cell Physiology
- Vol. 286 (5), C1053-C1061
- https://doi.org/10.1152/ajpcell.00418.2003
Abstract
Cytochrome c expression and mitochondrial biogenesis can be invoked by elevated intracellular Ca2+in muscle cells. To characterize the potential role of Ca2+as a messenger involved in mitochondrial biogenesis in muscle, we determined the effects of the Ca2+ionophore A-23187 on the expression of nuclear- and mitochondrially encoded genes. Treatment of myotubes with 1 μM A-23187 for 48–96 h increased nuclear-encoded β-subunit F1ATPase 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 Ca2+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 β-subunit F1ATPase mRNA. These results indicate that changes in intracellular Ca2+can modify mitochondrial phenotype, in part via the involvement of Egr-1.Keywords
This publication has 41 references indexed in Scilit:
- Mitochondrial Transcription Factor A and Its Downstream Targets Are Up-regulated in a Rat HepatomaPublished by Elsevier BV ,2002
- Regulation of Mitochondrial Biogenesis in Skeletal Muscle by CaMKScience, 2002
- Contractile Activity-induced Transcriptional Activation of Cytochrome c Involves Sp1 and Is Proportional to Mitochondrial ATP Synthesis in C2C12 Muscle CellsPublished by Elsevier BV ,2001
- Interplay of Sp1 and Egr-1 in the Proximal Platelet-derived Growth Factor A-Chain Promoter in Cultured Vascular Endothelial CellsJournal of Biological Chemistry, 1995
- The role of thyroid hormone and promoter diversity in the regulation of nuclear encoded mitochondrial proteinsBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1995
- Expression and fate of the nuclearly encoded subunits of cytochrome-c oxidase in cultured human cells depleted of mitochondrial gene productsBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1995
- Effect of hypothyroidism on the expression of cytochrome c and cytochrome c oxidase in heart and muscle during developmentMolecular and Cellular Biochemistry, 1995
- Regulation by thyroid hormone of nuclear and mitochondrial genes encoding subunits of cytochrome-c oxidase in rat liver and skeletal muscleMolecular Endocrinology, 1992
- Chronic long‐term electrostimulation creates a unique metabolic enzyme profile in rabbit fast‐twitch muscleFEBS Letters, 1989
- Chronic stimulation of rat skeletal muscle induces coordinate increases in mitochondrial and nuclear mRNAs of cytochrome‐c‐oxidase subunitsEuropean Journal of Biochemistry, 1989