Mitochondrial ferritin in the substantia nigra in restless legs syndrome

J Neuropathol Exp Neurol. 2009 Nov;68(11):1193-9. doi: 10.1097/NEN.0b013e3181bdc44f.


Restless legs syndrome (RLS) is a neurological disorder that is thought to involve decreased iron availability in the brain. Iron is required for oxidative metabolism and plays a critical role in redox reactions in mitochondria. The recent discovery of mitochondrial ferritin (FtMt) provided the opportunity to identify a potential correlation between iron and mitochondrial function in RLS. Human substantia nigra (SN) and putamen autopsy samples from 8 RLS cases and 8 controls were analyzed. Mitochondrial ferritin levels in RLS SN tissue homogenate samples assessed by immunoblots had more FtMt than control samples (p < 0.01), whereas there were no significant differences in FtMt in the putamen samples. By immunohistochemistry, neuromelanin-containing neurons in the SN were the predominant cell type expressing FtMt. Staining in neurons in RLS samples was consistently greater than that in controls. Cytochrome c oxidase staining, which reflects numbers of mitochondria, showed a similar staining pattern to that of FtMt, whereas there was less immunostaining in the RLS cases for cytosolic H-ferritin. These results suggest that increased numbers of mitochondria in neurons in RLS and increased FtMt might contribute to insufficient cytosolic iron levels in RLS SN neurons; they are consistent with the hypothesis that energy insufficiency in these neurons may be involved in the pathogenesis of RLS.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cytosol / chemistry
  • Cytosol / metabolism
  • Female
  • Ferritins / biosynthesis
  • Ferritins / metabolism*
  • Humans
  • Iron / deficiency
  • Iron / metabolism
  • Male
  • Middle Aged
  • Mitochondrial Proteins / biosynthesis
  • Mitochondrial Proteins / metabolism*
  • Neurons / chemistry
  • Neurons / metabolism
  • Restless Legs Syndrome / metabolism*
  • Restless Legs Syndrome / pathology
  • Substantia Nigra / chemistry
  • Substantia Nigra / metabolism*
  • Substantia Nigra / pathology


  • Mitochondrial Proteins
  • Ferritins
  • Iron