Hanyang Med Rev.  2013 May;33(2):104-109. 10.7599/hmr.2013.33.2.104.

Reactive Oxygen Species and Cellular Function Switch

• Ryu SE

• KMID: 2168240
• DOI: http://doi.org/10.7599/hmr.2013.33.2.104

Abstract

Reactive oxygen species (ROS) are harmful to cellular components such as proteins, DNA and lipids. The continuous production of ROS during the respiratory electron transfer process has been regarded as the major cause of aging. However, the discoveries of proteins whose structure and function switch with cellular ROS suggest that ROS are active players in cellular regulation. OxyR is the first protein whose ROS-regulated mechanism was revealed by the atomic structure studies. The distantly-located two cysteines in OxyR form a disulfide bond by reaction with ROS, resulting in conformational and functional switches in the protein. The heat shock protein 33 is another protein that is activated by increased level of cellular ROS. Many other cellular proteins including protein tyrosine phosphatases are also regulated by ROS. This review focuses on the structure and function of the ROS-regulated proteins and their implications on the ROS's cellular roles. Detailed studies on the ROS-generating protein machinery and the ROS-regulated proteins should contribute to the therapeutic control of ROS-related diseases and aging processes.

Keyword

Reactive Oxygen Species; OxyR; Hsp33; Protein Tyrosine Phosphatase; Protein Structure

MeSH Terms

Aging
DNA
Electrons
Heat-Shock Proteins
Protein Tyrosine Phosphatases
Proteins
Reactive Oxygen Species
DNA
Heat-Shock Proteins
Protein Tyrosine Phosphatases
Proteins
Reactive Oxygen Species

Figure

• 

  Fig. 1 ROS's cellular function regulation network. The mitochondria-derived ROS play two roles including cellular function regulation and promotion of diseases/aging. The cellular function regulation by ROS is likely to feedback its results to mitochondria, resulting in the control of ROS generation level. It will be necessary to understand the balance between the ROS's effects on diseases/aging and the cellular function regulation.

• 

  Fig. 2 ROS-mediated structural switch in OxyR. The reduced OxyR (left-hand side) has two cysteines (Cys199 and Cys208) that are distant to each other (the inter-sulfur atom distance: 17 Å). ROS oxidize the two cysteines, resulting in a disulfide bond of the oxidized OxyR (right-hand side). For the disulfide bond formation, two cysteines travel to a close location to each other, causing large structural transitions that affect the monomeric and dimeric interaction surfaces and promote the oxidized OxyR-mediated transcription of antioxidant proteins.

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