Manganese Superoxide Dismutase: Guardian of the Powerhouse

Abstract

The mitochondrion is vital for many metabolic pathways in the cell, contributing all or important constituent enzymes for diverse functions such as β-oxidation of fatty acids, the urea cycle, the citric acid cycle, and ATP synthesis. The mitochondrion is also a major site of reactive oxygen species (ROS) production in the cell. Aberrant production of mitochondrial ROS can have dramatic effects on cellular function, in part, due to oxidative modification of key metabolic proteins localized in the mitochondrion. The cell is equipped with myriad antioxidant enzyme systems to combat deleterious ROS production in mitochondria, with the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD) acting as the chief ROS scavenging enzyme in the cell. Factors that affect the expression and/or the activity of MnSOD, resulting in diminished antioxidant capacity of the cell, can have extraordinary consequences on the overall health of the cell by altering mitochondrial metabolic function, leading to the development and progression of numerous diseases. A better understanding of the mechanisms by which MnSOD protects cells from the harmful effects of overproduction of ROS, in particular, the effects of ROS on mitochondrial metabolic enzymes, may contribute to the development of novel treatments for various diseases in which ROS are an important component.

Peroxisome Proliferator-activated Receptor γ Co-activator 1-α as a Critical Co-activator of the Murine Hepatic Oxidative Stress Response and Mitochondrial Biogenesis in Staphylococcus aureus Sepsis

“…In particular, SOD-2 up-regulation and increased superoxide scavenging modulate damage to mtDNA and dysfunction of the TCA cycle and the electron transport chain (39).…”

Oxidative stress in oocytes during midprophase induces premature loss of cohesion and chromosome segregation errors

“…We also investigated the effect of SOD2 KD on chromosome segregation in Drosophila oocytes because mitochondria are the main producers of ROS in the cell and SOD2 is the primary scavenger of superoxide in the mitochondrial matrix (50). Moreover, several lines of evidence indicate that when SOD2 activity is decreased, elevation of ROS is not restricted to the mitochondria.…”

Mitochondrial Free Radicals, Antioxidants, Nutrient Substances, and Chronic Hepatitis C

“…In turn, hydroxyl radical and nitric dioxide can be produced from ONOO -, and membrane lipid peroxidation and nitration of proteins on tyrosine residues are promoted (Beckman and Crow, 1993). ONOOfurther damages complex I, II, and V as well as mitochondrial SOD, GPx, and aconitase (Holley et al, 2011). A growing body of evidence demonstrates that NO diffuses easily along its gradient into mitochondria and that NO is also produced by mitochondria (Alvarez et al, 2003).…”