Increased mitochondrial gene expression during L6 cell myogenesis is accelerated by insulin

Int J Biochem Cell Biol. 2005 Sep;37(9):1815-28. doi: 10.1016/j.biocel.2005.02.008. Epub 2005 Mar 11.

Abstract

Insulin is the most potent anabolic hormone. The greatest sensitivity to insulin is exhibited by muscle, liver and adipose cells. To study links between insulin and mitochondrial function over the course of cellular quiescence and differentiation, we quantified mitochondrial RNA and DNA in L6 myoblasts and HTC-IR hepatocytes cultured under low-serum conditions in the presence of insulin. The expression of the whole set of mitochondrial genes was determined using reverse transcriptase (RT)-real time PCR. Cell proliferation was assayed by the incorporation of (3)H-thymidine and myoblast differentiation was analyzed by morphological and biochemical markers of myogenesis. Low growth factor concentration in medium decreased proliferation of both cell types and induced differentiation of myoblasts. The expression of all mitochondrial genes decreased in quiescent hepatocytes whereas it increased in quiescent differentiated myotubes, as compared with proliferating cells, similarly to reflecting the expression of the insulin receptor gene, both in myoblasts and hepatocytes. The kinetics of mitochondrial RNA levels were similar to the expression patterns of two nuclear genes, subunit e of mitochondrial ATP-synthase and uncoupling protein-2; however, they did not reflect changes in mitochondrial DNA content. Insulin accelerated myogenesis and expression of both mitochondrial and nuclear genes in differentiated myotubes but not in quiescent hepatocytes. Our studies prove that myogenesis may require the orchestrated transcriptional activation of both mitochondrial and nuclear genes and provide additional evidence confirming the regulatory impact of insulin on the function of muscle mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • DNA, Mitochondrial / metabolism*
  • Gene Expression
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hypoglycemic Agents / pharmacology*
  • Insulin / pharmacology*
  • Ion Channels
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Membrane Transport Proteins / metabolism
  • Mitochondria, Muscle / genetics*
  • Mitochondrial Proteins / metabolism
  • Mitochondrial Proton-Translocating ATPases / metabolism
  • Muscle Development / physiology*
  • Myoblasts / drug effects*
  • Myoblasts / metabolism
  • RNA / metabolism*
  • RNA, Mitochondrial
  • Rats
  • Uncoupling Protein 2

Substances

  • DNA, Mitochondrial
  • Hypoglycemic Agents
  • Insulin
  • Ion Channels
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • RNA, Mitochondrial
  • Ucp2 protein, rat
  • Uncoupling Protein 2
  • RNA
  • Mitochondrial Proton-Translocating ATPases