Intermittent increases in cytosolic Ca2+ stimulate mitochondrial biogenesis in muscle cells

Edward O. Ojuka, Terry E. Jones, Dong Ho Han, May Chen, Brian R. Wamhoff, Michael Sturek, John O. Holloszy

Research output: Contribution to journalArticle

65 Scopus citations


Muscle contractions cause numerous disturbances in intracellular homeostasis. This makes it impossible to use contracting muscle to identify which of the many signals generated by contractions are responsible for stimulating mitochondrial biogenesis. One purpose of this study was to evaluate the usefulness of L6 myotubes, which do not contract, for studying mitochondrial biogenesis. A second purpose was to evaluate further the possibility that increases in cytosolic Ca2+ can stimulate mitochondrial biogenesis. Continuous exposure to 1 μM ionomycin, a Ca2+ ionophore, for 5 days induced an increase in mitochondrial enzymes but also caused a loss of myotubes, as reflected in an ∼40% decrease in protein per dish. However, intermittent (5 h/day) exposure to ionomycin, or to caffeine or W7, which release Ca2+ from the sarcoplasmic reticulum, did not cause a decrease in protein per dish. Raising cytosolic Ca2+ intermittently with these agents induced significant increases in mitochondrial enzymes. EGTA blocked most of this effect of ionomycin, whereas dantrolene, which blocks Ca2+ release from the sarcoplasmic reticulum, largely prevented the increases in mitochondrial enzymes induced by W7 and caffeine. These findings provide evidence that intermittently raising cytosolic Ca2+ stimulates mitochondrial biogenesis in muscle cells.

Original languageEnglish (US)
Pages (from-to)E1040-E1045
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number5 46-5
StatePublished - Nov 1 2002


  • Caffeine
  • Exercise
  • Gene expression
  • Ionomycin
  • L6 myotubes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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