Chronic exposure of neural cells to elevated intracellular sodium decreases mitochondrial mRNA expression

Krish Chandrasekaran, Li Ing Liu, Kimmo Hatanpää, Umesha Shetty, Zara Mehrabian, Peter D. Murray, Gary Fiskum, Stanley I. Rapoport

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Regulation of expression of mitochondrial DNA- (mtDNA-) encoded genes of oxidative phosphorylation can occur rapidly in neural cells subjected to a variety of physiological and pathological conditions. However, the intracellular signal(s) involved in regulating these processes remain unknown. Using mtDNA-encoded cytochrome oxidase subunit III (COX III), we show that its mRNA expression in a differentiated rat pheochromocytoma cell line PC12S is decreased by chronic exposure to agents that increase intracellular sodium. Treatment of differentiated PC12S cells either with ouabain, an inhibitor of Na/K-ATPase, or with monensin, a sodium ionophore, decreased the steady-state levels of COX III mRNA by 50%, 3-4 h after addition of the drugs. No significant reduction in mtDNA-encoded 12S rRNA or nuclear DNA-encoded β-actin mRNA were observed. Removal of the drugs restored the normal levels of COX III mRNA. Determination of half-lives of COX III mRNA, 12S rRNA, and β-actin mRNA revealed a selective decrease in the half-life of COX III mRNA from 3.3 h in control cells to 1.6 h in ouabain-treated cells, and to 1 h in monensin-treated cells. These results suggest the existence of a mechanism of posttranscriptional regulation of mitochondrial gene expression that is independent of the energetic status of the cell and may operate under pathological conditions.

Original languageEnglish (US)
Pages (from-to)141-150
Number of pages10
JournalMitochondrion
Volume1
Issue number2
DOIs
StatePublished - Aug 1 2001

Keywords

  • Intracellular sodium
  • Mitochondrial mRNA
  • Neural cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Chandrasekaran, K., Liu, L. I., Hatanpää, K., Shetty, U., Mehrabian, Z., Murray, P. D., Fiskum, G., & Rapoport, S. I. (2001). Chronic exposure of neural cells to elevated intracellular sodium decreases mitochondrial mRNA expression. Mitochondrion, 1(2), 141-150. https://doi.org/10.1016/S1567-7249(01)00010-1