title: MnSOD in oxidative stress response-potential regulation via mitochondrial protein influx.
abstract: CONCLUSIONS
  The mitochondrial antioxidant manganese superoxide dismutase (MnSOD) is encoded by genomic DNA and its dismutase function is fully activated in the mitochondria to detoxify free radical O2(•-) generated by mitochondrial respiration. Accumulating evidence shows an extensive communication between the mitochondria and cytoplasm under oxidative stress. Not only is the MnSOD gene upregulated by oxidative stress, but MnSOD activity can be enhanced via the mitochondrial protein influx (MPI).
  
  
  BACKGROUND
  A cluster of MPI containing cytoplasmic/nuclear proteins, such as cyclins, cyclin-dependent kinases, and p53 interact with and alter MnSOD activity. These proteins modulate MnSOD superoxide scavenging activity via post-translational modifications in the mitochondria. In addition to well-established pathways in gene expression, recent findings suggest that MnSOD enzymatic activity can also be enhanced by phosphorylation of specific motifs in mitochondria. This review attempts to discuss the pre- and post-translational regulation of MnSOD, and how these modifications alter MnSOD activity, which induces a cell adaptive response to oxidative stress.
  
  
  RESULTS
  MnSOD is biologically significant to aerobic cells. Its role in protecting the cells against the deleterious effects of reactive oxygen species is evident. However, the exact network of MnSOD-associated cellular adaptive reaction to oxidative stress and its post-translational modifications, especially its enzymatic enhancement via phosphorylation, is not yet fully understood.
  
  
  CONCLUSIONS
  The broad discussion of the multiple aspects of MnSOD regulation, including gene expression, protein modifications, and enzymatic activity, will shed light onto the unknown mechanisms that govern the prosurvival networks involved in cellular and mitochondrial adaptive response to genotoxic environment.
authors.affiliation: 1 Department of Radiation Oncology, University of California Davis , Sacramento, California.
authors.forename: Demet
authors.initials: D
authors.lastname: Candas
authors.forename: Jian Jian
authors.initials: JJ
authors.lastname: Li
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D013482:Superoxide Dismutase / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D024101:Mitochondrial Proteins; D013482:Superoxide Dismutase; D016159:Tumor Suppressor Protein p53; D000099156:Superoxide Dismutase 2; C495901:TP53 protein, human