Article

Acetylation of MnSOD directs enzymatic activity responding to cellular nutrient status or oxidative stress

Departments of Cancer Biology, Pediatrics, and Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Aging (Impact Factor: 6.43). 02/2011; 3(2):102-7.
Source: PubMed

ABSTRACT

A fundamental observation in biology is that mitochondrial function, as measured by increased reactive oxygen species (ROS), changes significantly with age, suggesting a potential mechanistic link between the cellular processes governing longevity and mitochondrial metabolism homeostasis. In addition, it is well established that altered ROS levels are observed in multiple age-related illnesses including carcinogenesis, neurodegenerative, fatty liver, insulin resistance, and cardiac disease, to name just a few. Manganese superoxide dismutase (MnSOD) is the primary mitochondrial ROS scavenging enzyme that converts superoxide to hydrogen peroxide, which is subsequently converted to water by catalase and other peroxidases. It has recently been shown that MnSOD enzymatic activity is regulated by the reversible acetylation of specific, evolutionarily conserved lysine(s) in the protein. These results, suggest for the first time, that the mitochondria contain bidirectional post-translational signaling networks, similar to that observed in the cytoplasm and nucleus, and that changes in lysine acetylation alter MnSOD enzymatic activity. In addition, these new results demonstrate that the mitochondrial anti-aging or fidelity / sensing protein, SIRT3, responds to changes in mitochondrial nutrient and/or redox status to alter the enzymatic activity of specific downstream targets, including MnSOD that adjusts and/or maintains ROS levels as well as metabolic homeostatic poise.

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Available from: Ozkan Ozden, Dec 19, 2014
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    • "SOD1 and SOD3 are Cu-Zn-SOD types, whereas SOD2 is Mn-SOD. Sirtuin, which was originally identified as a protein deacetylase[59], is also a regulator of the expression of cytoprotective enzymes such as SOD[60,61]and CAT (Fig. 4)[62]. Mammalian sirtuins consist of seven members (SIRT1–7), and have been implicated in various cellular responses including aging, transcription , apoptosis, and stress resistance[63]. "
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    • "In various studies, many investigators have characterized different SOD2 mutants to illustrate the biological function and structure–activity relationship of SOD2; however, nobody has acquired a mutant with activity higher than that of wild-type SOD2 [11] [12] [13] [14] [15]. In recent years, several studies have reported that the antioxidative activity of the SOD2 is regulated by many posttranslational modifications (PTMs), including acetylation [16] [17], methylation [18], phosphorylation [19], nitration [14] [20], and glutathionylation [20]. These explorations have provided new methods to possibly obtain a higher-activity mutant form of SOD2 by changing the PTMs in SOD2. "
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    • "Mutations within the MnSOD gene and its regulatory sequence have been observed in several types of human cancers [5,38–40]. In addition to cancer, mutations in MnSOD are associated with cardiomyopathy and neuronal diseases, demonstrating the significant role of MnSOD activity in agerelated illnesses [6]. "
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