The essential role of mitochondria in the biogenesis of cellular iron-sulfur proteins

Biol Chem. 1999 Oct;380(10):1157-66. doi: 10.1515/BC.1999.147.

Abstract

Iron-sulfur (Fe/S) proteins play an important role in electron transfer processes and in various enzymatic reactions. In eukaryotic cells, known Fe/S proteins are localised in mitochondria, the cytosol and the nucleus. The biogenesis of these proteins has only recently become the focus of investigations. Mitochondria are the major site of Fe/S cluster biosynthesis in the cell. The organelles contain an Fe/S cluster biosynthesis apparatus that resembles that of prokaryotic cells. This apparatus consists of some ten proteins including a cysteine desulfurase producing elemental sulfur for biogenesis, a ferredoxin involved in reduction, and two chaperones. The mitochondrial Fe/S cluster synthesis apparatus not only assembles mitochondrial Fe/S proteins, but also initiates formation of extra-mitochondrial Fe/S proteins. This involves the export of sulfur and possibly iron from mitochondria to the cytosol, a reaction performed by the ABC transporter Atm1p of the mitochondrial inner membrane. A possible substrate of Atm1p is an Fe/S cluster that may be stabilised for transport. Constituents of the cytosol involved in the incorporation of the Fe/S cluster into apoproteins have not been described yet. Many of the mitochondrial proteins involved in Fe/S cluster formation are essential, illustrating the central importance of Fe/S proteins for life. Defects in Fe/S protein biogenesis are associated with the abnormal accumulation of iron within mitochondria and are the cause of an iron storage disease.

Publication types

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

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Cell Nucleus / metabolism
  • Cytosol / metabolism
  • Humans
  • Intracellular Membranes / metabolism
  • Iron-Sulfur Proteins / biosynthesis*
  • Mitochondria / metabolism*
  • Saccharomyces cerevisiae / metabolism

Substances

  • ATP-Binding Cassette Transporters
  • Iron-Sulfur Proteins