Subcellular Distribution of Superoxide Dismutases (SOD) in Rat Liver

By A. Okado-Matsumoto, I. Fridovich. Journal of Biological Chemistry, 2001

1,019 citations recorded by the source corpus.

Rat liver was homogenized in isotonic buffer, fractionated by differential centrifugation, and then subfractionated by equilibrium sedimentation in Nycodenz gradients. Fractions were assayed for both Cu,Zn-superoxide dismutase (SOD) and Mn-SOD by exploiting the cyanide sensitivity of the former activity and by the use of specific antibodies. As expected, the cytosol and lysosomal fractions contained Cu,Zn-SOD; while the mitochondrial matrix contained Mn-SOD. In mitochondria, Cu,Zn-SOD was found in the intermembrane space and Mn-SOD in the matrix and also on the inner membrane. The Mn-SOD associated with the inner membrane was solubilized by 0.5 m NaCl. Surprisingly the intracellular membrane fraction (microsomes) contained bound Cu,Zn-SOD that could be solubilized with a detergent, and to lesser degree with 0.5m NaCl. Both the cytosolic and mitochondrial Cu,Zn-SODs were isolated and compared. They have identical molecular mass, cyanide sensitivity, SDS sensitivity, heat stability, and chloroform + ethanol stability. Tissue from Cu,Zn-SOD knockout mice was entirely devoid of Cu,Zn-SOD; indicating that the cytosolic and the intermembrane space Cu,Zn-SODs are coded for by the same gene. The significance of this distribution of the SODs is discussed.

Subfields: Molecular Biology, Nutrition and Dietetics, Oncology

View Paper: https://www.semanticscholar.org/paper/28674211fa3b957af63b47432055273ca4a42ea0

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. Douglas C. Wallace
2. A. Navarro
3. Y. Bae
4. Hyunjin Oh
5. Young Do Yoo
6. S. Rhee
7. J. Turrens
8. J. Min

In Nutrition and Dietetics

1. Douglas C. Wallace
2. J. Turrens

In Oncology

1. Douglas C. Wallace
2. J. Turrens

Citations in the corpus

• Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. (2014, background): “O2 · formed in the mitochondria is dismuted to H2O2 by Cu-Zn-SOD present in the mitochondrial intermembranous space and Mn-SOD present in the mitochondrial matrix (213).”
• Is the Oxidative Stress Theory of Aging Dead? (2009, neutral): “CuZnSOD (Sod1) is themajor superoxide dismutase isozyme found in cells and is localized in the cytosol and the intermembrane space of the mitochondria [24,25].”
• Regulation of reactive oxygen species generation in cell signaling (2011, background): “chondrial matrix or by Cu, Zn-SOD in the IMS of mitochondria (Okado-Matsumoto and Fridovich, 2001; Sturtz et al., 2001; Weisiger and Fridovich, 1973a; 1973b).”
• The changing faces of glutathione, a cellular protagonist. (2003, background): “Superoxide released into the IMS can be eliminated by a different SOD isoenzyme (Cu, ZnSOD, or SOD1), which is found in the cytoplasm of eukaryotic cells, or scavenged by cytochrome c plus cytochrome c oxidase system (Okado-Matsumoto and Fridovich, 2001).”
• Trends in oxidative aging theories. (2007, background): “CuZnSOD knockout CuZnSOD is the major cytoplasmic superoxide scavenger [180] and is also found in the mitochondrial intermembrane space [181,182].”
• Oxidative Stress, Mitochondrial Dysfunction, and Aging (2011, background): “Most aging theories postulate a single physiological cause of aging, and likely these theories are correct to a certain degree and in certain aspects of aging.”
• Oxidants, antioxidants and the ischemic brain (2004, background): “Cu,Zn-SOD (SOD1) is principally found in the cytosolic and lysosomal fractions, but is also in the mitochondrial intermembrane space (Okado-Matsumoto and Fridovich, 2001).”
• Mitochondrial formation of reactive oxygen species (2003, background): “Firstly, this compartment contains a different SOD isozyme which contains copper and zinc instead of manganese (CuZnSOD (Okado-Matsumoto & Fridovich, 2001)) and is also found in the cytoplasm of eukaryotic cells.”
• Superoxide Dismutases: Role in Redox Signaling, Vascular Function, and Diseases (2011, neutral): “It exists as a 32kDa homodimer and is mainly localized in the cytosol with a smaller fraction in the inter-membrane space (IMS) of mitochondria (42, 175, 213).”
• The mitochondrial energy transduction system and the aging process. (2007, background): “membrane, and with the Cu,Zn-SOD of the intermembrane space (123).”
• A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine (2005, background): “Import of Cu/ZnSOD into the mitochondrial intermembrane space occurs as the apoprotein, which is metallated upon entrance into the intermembrane space by the CCS metallochaperone (166, 207).”
• Copper, oxidative stress, and human health. (2005, background): “CuZn-SOD is found in the cytosol, nucleus, and the intermembrane space of mitochondria (Okado-Matsumoto and Fridovich, 2001), while manganese (Mn) SOD (SOD2) is found primarily in the mitochondrial matrix.”