Manganese activation of superoxide dismutase 2 in the mitochondria of Saccharomyces cerevisiae

Edward Luk, Mei Yang, Laran T. Jensen, Yves Bourbonnais, Valeria Cizewski Culotta

Research output: Contribution to journalArticlepeer-review

Abstract

Manganese-dependent superoxide dismutase 2 (SOD2) in the mitochondria plays a key role in protection against oxidative stress. Here we probed the pathway by which SOD2 acquires its manganese catalytic cofactor. We found that a mitochondrial localization is essential. A cytosolic version of Saccharomyces cerevisiae Sod2p is largely apo for manganese and is only efficiently activated when cells accumulate toxic levels of manganese. Furthermore, Candida albicans naturally produces a cytosolic manganese SOD (Co SOD3), yet when expressed in the cytosol of S. cerevisiae, a large fraction of Co SOD3 also remained manganese-deficient. The cytosol of S. cerevisae cannot readily support activation of Mn-SOD molecules. By monitoring the kinetics for metalation of S. cerevisiae Sod2p in vivo, we found that prefolded Sod2p in the mitochondria cannot be activated by manganese. Manganese insertion is only possible with a newly synthesized polypeptide. Furthermore, Sod2p synthesis appears closely coupled to Sod2p import. By reversibly blocking mitochondrial import in vivo, we noted that newly synthesized Sod2p can enter mitochondria but not a Sod2p polypeptide that was allowed to accumulate in the cytosol. We propose a model in which the insertion of manganese into eukaryotic SOD2 molecules is driven by the protein unfolding process associated with mitochondrial import.

Original languageEnglish (US)
Pages (from-to)22715-22720
Number of pages6
JournalJournal of Biological Chemistry
Volume280
Issue number24
DOIs
StatePublished - Jun 17 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Manganese activation of superoxide dismutase 2 in the mitochondria of Saccharomyces cerevisiae'. Together they form a unique fingerprint.

Cite this