Differential localization and potency of manganese porphyrin superoxide dismutase-mimicking compounds in Saccharomyces cerevisiae
Document Type
Article
Abstract
Cationic Mn(III) porphyrin complexes based on MnTM-2-PyP are among the most promising superoxide dismutase (SOD) mimicking compounds being considered as potential anti-inflammatory drugs. We studied four of these active compounds in the yeast Saccharomyces cerevisiae, MnTM-2-PyP, MnTE-2-PyP, MnTnHex-2-PyP, and MnTnBu-2-PyP, each of which differs only in the length of its alkyl substituents. Each was active in improving the aerobic growth of yeast lacking SOD (sod1δ) in complete medium, and the efficacy of each mimic was correlated with its characteristic catalytic activity. We also studied the partitioning of these compounds between mitochondria and cytosol and found that the more hydrophobic members of the series accumulated in the mitochondria. Moreover, the degree to which a mimic mitigated the sod1δ auxotrophic phenotype for lysine relative to its auxotrophic phenotype for methionine depended upon its level of lipophilicity-dependent accumulation inside the mitochondria. We conclude that localization within the cell is an important factor in biological efficacy in addition to the degree of catalytic activity, and we discuss possible explanations for this effect.
Keywords
Lysine synthesis, Methionine synthesis, Mitochondria, Mn(III) N-alkylpyridylporphyrin, Oxidative stress, SOD mimic
Publication Date
1-1-2014
Publication Title
Redox Biology
ISSN
22132317
Volume
3
First Page
1
Last Page
6
PubMed ID
25462059
Digital Object Identifier (DOI)
10.1016/j.redox.2014.09.003
Recommended Citation
Li, Alice Ma; Martins, Jake; Tovmasyan, Artak; Valentine, Joan S.; Batinic-Haberle, Ines; Spasojevic, Ivan; and Gralla, Edith B., "Differential localization and potency of manganese porphyrin superoxide dismutase-mimicking compounds in Saccharomyces cerevisiae" (2014). Translational Neuroscience. 1264.
https://scholar.barrowneuro.org/neurobiology/1264