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. 2011;12(10):7114-62.
doi: 10.3390/ijms12107114. Epub 2011 Oct 21.

Manganese Superoxide Dismutase: Guardian of the Powerhouse

Free PMC article

Manganese Superoxide Dismutase: Guardian of the Powerhouse

Aaron K Holley et al. Int J Mol Sci. .
Free PMC article


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.

Keywords: cancer; cardiovascular disease; manganese superoxide dismutase; metabolism; mitochondria; neurodegenerative disorders; oxidative stress; reactive oxygen species.


Figure 1
Figure 1
Mitochondria are the major source of ROS in the cell through superoxide production at complexes I and III of the electron transport chain (center). Excessive ROS production can damage different components of mitochondrial metabolic pathways, resulting in altered mitochondrial function and an imbalance in cellular homeostasis (inner ring). Diminished mitochondrial function leads to the development of numerous diseases (outer ring).

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