Effect of IGF-1 on the balance between autophagy of dysfunctional mitochondria and apoptosis

FEBS Lett. 2004 Nov 19;577(3):357-60. doi: 10.1016/j.febslet.2004.10.040.


Mutations in mitochondrial DNA (mtDNA) cause excessive production of mitochondrial reactive oxygen species (ROS) and shorten animal life span. We examined the mechanisms responsible for removal of mitochondria with deleterious mtDNA mutations by autophagy. Incubation of primary cells and cell lines in the absence of serum promotes autophagy of mitochondria with deleterious mtDNA mutations but spares their normal counterparts. The effect of serum withdrawal on the autophagy of dysfunctional mitochondria is prevented by the addition of IGF-1. As a result of the elimination of mitochondria with deleterious mutations, excessive ROS production, characteristic of dysfunctional mitochondria, is greatly reduced. Mitochondrial autophagy shares a common mechanism with mitochondrial-induced cell apoptosis, including mitochondrial transition pore formation and increased ROS production.

Publication types

  • Comparative Study

MeSH terms

  • Apoptosis*
  • Autophagy*
  • Cell Line, Tumor
  • Cells, Cultured
  • Culture Media, Serum-Free
  • DNA, Mitochondrial / genetics
  • Fibroblasts / metabolism
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Insulin-Like Growth Factor I / pharmacology*
  • MELAS Syndrome / genetics
  • MELAS Syndrome / metabolism
  • Mitochondria / drug effects
  • Mitochondria / pathology*
  • Mutation
  • Osteosarcoma
  • Oxidants / pharmacology
  • Reactive Oxygen Species / metabolism
  • Serum / metabolism
  • Time Factors


  • Culture Media, Serum-Free
  • DNA, Mitochondrial
  • Oxidants
  • Reactive Oxygen Species
  • Insulin-Like Growth Factor I
  • Hydrogen Peroxide