Serum suppresses myeloid progenitor apoptosis by regulating iron homeostasis

J Cell Biochem. 2001 Apr;82(1):171-86. doi: 10.1002/jcb.1111.


The growth and survival of committed hematopoietic progenitors is dependent upon cytokine signaling. However, serum is also required for optimal growth of these progenitors in culture ex vivo. Here we report that serum withdrawal leads to myeloid progenitor cell apoptosis. Although serum deprivation-induced cell death has many hallmarks typical of apoptosis, these cell deaths were not inhibited by hemopoietins, survival factors such as IGF-I, or treatment with a broad-spectrum caspase inhibitor. Rather, apoptosis due to serum withdrawal was associated with damage to mitochondria. Surprisingly the serum factor required for myeloid cell survival was identified as iron, and loss of iron led to marked reductions in ATP production. Furthermore, supplementing serum-deprived myeloid cells with bound or free iron promoted cell survival and prevented mitochondrial damage. Therefore, serum suppresses hematopoietic cell apoptosis by providing an obligate source of iron and iron homeostasis is critical for proper myeloid cell metabolism and survival.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Caspases / metabolism
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Culture Media, Serum-Free / chemistry
  • Culture Media, Serum-Free / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology
  • Interleukin-3 / chemistry
  • Interleukin-3 / pharmacology
  • Iron / metabolism*
  • Iron / pharmacology
  • Iron Deficiencies*
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Myeloid Progenitor Cells / cytology
  • Myeloid Progenitor Cells / drug effects
  • Myeloid Progenitor Cells / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / pharmacology


  • Culture Media, Serum-Free
  • Interleukin-3
  • Proto-Oncogene Proteins c-bcl-2
  • Insulin-Like Growth Factor I
  • Adenosine Triphosphate
  • Iron
  • Caspases