COMMENTARY

Balancing the generation and elimination of reactive oxygen species

Rusty Rodriguez*† and Regina Redman‡§ *U.S. Geological Survey, Western Fisheries Research Center, Seattle, WA 98115; ‡Department of Biology, University of Washington, Seattle, WA 98195; and §Department of Microbiology, Montana State University, Bozeman, MT 59717

ossil records suggest that bacte- ria developed the ability to photosynthesize Ϸ3,500 million years ago (mya), initiating a veryF slow accumulation of atmospheric oxygen (1). Recent geochemical models suggest that atmospheric oxygen did not accumulate to levels conducive for aerobic life until 500–1,000 mya (2, 3). The oxygenation of Earth’s atmosphere Fig. 1. Generation of different ROS by energy transfer or sequential univalent reduction of ground-state resulted in the emergence of aerobic triplet oxygen (from ref. 5). organisms followed by a great diversifi- cation of biological species and the eventual evolution of humans. also a major component of structural extremes, dehydration, salt, UV light, proteins in animals and plants and a ozone, and heavy metals, ROS are pro- Oxygen: A Gas to Love and Fear known osmoprotectant capable of miti- duced (11). In fact, the generation of Although oxygen is thought to have gating the impacts of drought, salt, and ROS is the only event known to be been responsible for the expansion of temperature stress in plants. Based on common among such divergent stresses. life on Earth, there are two sides to this the work of Chen and Dickman, proline When an abiotic stress induces an oxida- molecule: life giving and life taking. Ox- can now be added to an elite list of non- tive environment, organisms produce ygen in the air we breathe is a relatively enzymatic antioxidants that microbes, antioxidation systems to decrease the nonreactive chemical (4). However, animals, and plants require to mitigate concentration of toxic intracellular ROS. when oxygen is exposed to high-energy the impacts of ROS. Chen and Dickman (8) demonstrate that or electron-transferring chemical reac- The ROS story is complicated by the the ROS scavenging property of proline tions, it can be converted to various fact that plants and animals also have prevents the induction of programmed highly reactive chemical forms (Fig. 1) evolved mechanisms that capitalize on cell death by ROS generated during nu- collectively designated ‘‘reactive oxygen the toxic property of ROS to combat tritional stress. In addition, proline pro- species’’ (ROS; ref. 5). ROS are toxic to tects fungal cells against other abiotic biological organisms because they oxi- stresses such as UV light, heat, salt, and dize lipids, proteins, DNA, and carbohy- The amino acid hydrogen peroxide. There may be func- drates, resulting in the breakdown of tional roles such as signaling or sensing normal cellular, membrane, and repro- proline is a potent for ROS during exposure to abiotic ductive functions. Ultimately, toxic lev- stress, but none have been confirmed. els of ROS cause a chain reaction of scavenger of reactive cellular oxidation, resulting in disease Insight into the Evolution of Symbiosis and lethality (5–7). ROS are unavoid- oxygen species. One of the more interesting aspects of the able byproducts of biochemical pathways, work by Chen and Dickman (8) is the such as glycolysis and photosynthesis, possibility that it may reveal an elusive that are central to energy production pathogens. For example, when plants mechanism responsible for the ability of and storage strategies of aerobic mi- are exposed to microbial pathogens, symbiotic fungi to protect plants against crobes, animals, and plants (4, 5). As a they produce ROS that induce pro- abiotic and biotic stress. Fossil records result, aerobic organisms have evolved grammed cell death in the plant cells indicate that fungi have been associated enzymatic and nonenzymatic antioxida- surrounding the infection site to effec- with plants for Ͼ400 mya (12–14), and it tion mechanisms to eliminate ROS and tively ‘‘wall off’’ the pathogen and ter- is theorized that these recordings repre- avoid oxidative destruction. The growth minate the disease process (5). ROS sent early symbiotic interactions that were and reproduction of all aerobic pro- may also be transmitted through the responsible for the establishment of land karyotes and eukaryotes require a bal- phloem to distant plant tissues signaling plants (15). Since the first description of ance between the generation of ROS a pathogen attack (10). In these exam- plant͞fungal symbiosis (16, 17), all plants and the capacity of antioxidation sys- ples, ROS act locally as toxin and dis- studied in natural ecosystems have been tems to eliminate them. It is noteworthy tantly as signaling molecules. However, found to be symbiotic with fungi (18). when novel antioxidation systems are it appears that ROS have a number of Fungal symbionts may express a variety of identified. In this issue of PNAS, Chen other potential biochemical functions lifestyles, including parasitism, mutualism, and Dickman (8) demonstrate that the such as biochemical signaling, gene ex- amino acid proline is a potent scavenger pression, protein inhibition, environmental of ROS. Unlike other amino acids, pro- sensing, and activation of transcription See companion article on page 3459. line has a cyclized amino nitrogen that factors (4–7, 11). †To whom correspondence should be addressed. E-mail: has significant influence on the confor- When organisms are exposed to rusty࿝[email protected]. mation of polypeptides (9). Proline is abiotic stresses such as temperature © 2005 by The National Academy of Sciences of the USA

www.pnas.org͞cgi͞doi͞10.1073͞pnas.0500367102 PNAS ͉ March 1, 2005 ͉ vol. 102 ͉ no. 9 ͉ 3175–3176 Downloaded by guest on October 2, 2021 or commensalism that decrease, increase, erty of proline. All of the abiotic stresses possible that symbiotic fungi prompt or have no effect on host fitness, respec- listed above result in the production of plants to activate the biosynthesis of tively (19). However, in natural ecosys- ROS, and Chen and Dickman demon- proline to scavenge ROS generated by tems, pathogenic symbioses are the excep- strate that proline protects fungi against stress. tion, and nonpathogenic symbioses are the these stresses (dehydration and pathogen The ramifications of the work by rule. Fitness benefits conferred to host attack were not tested). Therefore, symbi- Chen and Dickman (8) go beyond the plants by fungal mutualists include toler- otically conferred stress tolerance may be realm of fungi, because it addresses a ance to abiotic and biotic stresses such as based on ROS generation, the one com- fundamental aspect of evolution, how temperature extremes, dehydration, salt, mon aspect of stress. Mutualistic fungi cells balance the generation, and elimi- UV light, heavy metals, and pathogen allow symbiotic plants to perceive stress nation of ROS. Based on this work, the attack (20–24). However, the mecha- more quickly than nonsymbiotic plants, role of proline as a ROS scavenger, and nism(s) responsible for symbiotically con- resulting in the rapid and strong activation its ability to mitigate the impacts of ferred stress tolerance are poorly defined, of plant biochemical reactions that miti- abiotic stress should be evaluated across and none focus on the antioxidation prop- gate the impacts of stress (23, 25). It is all evolutionary lineages.

1. Schopf, J. W. (1993) Science 260, 640–646. 11. Mittler, R & Zilinskas, B. A. (2004) in Molecular 19. Lewis, D. H. (1985) in The Biology of Mutualism, 2. Kah, L. C., Lyons, T. W. & Frank, T. D. (2004) Ecotoxicology of Plants, ed. Sandermann, H. ed. Boucher, D. H. (Croom Helm, London), pp. Nature 431, 834–838. (Springer, Berlin), pp. 51–73. 29–39. 3. Canfield, D.E. & Teske, A. (1996) Nature 382, 12. Simon, L., Bousquet, J., Levesque, R. C. & La- 20. Stone, J. K., Bacon, C. W. & White, J. F. (2000) in 127–132. londe, M. (1993) Nature 363, 67–69. Microbial Endophytes, eds. Bacon, C.W. & White, 4. Cadens, E. (1989) Annu. Rev. Biochem. 58, 79– 13. Remy, W., Taylor, T. N., Hass, H. & Kerp, H. J. F. J. (Dekker, New York), pp. 3–30. 110. (1994) Proc. Nat. Acad. Sci. 91, 11841–11843. 21. Read, D. J. (1999) in Mycorrhiza, eds. Varma, A. 5. Apel, K. & Hirt, H. (2004) Annu. Rev. Plant Biol. 14. Redecker, D., Kodner, R. & Graham, L. E. (2000) & Hock, B. (Springer, Berlin), pp. 3–34. 55, 373–399. Science 289, 1920–1921. 22. Schardl, C. L., Leuchtmann, A. & Spiering, M. J. 6. Valko, M., Izakovic, M., Mazur, M., Rhodes, C. J. 15. Pirozynski, K. A. & Malloch, D. W. (1975) Bio- (2004) Annu. Rev. Plant Biol. 55, 315–340. & Telser, J. (2004) Mol. Cell. Biochem. 266, 37–56. Systems 6, 153–164. 23. Rodriguez, R., Redman, R. & Henson, J. M. 7. Harper, M. E., Bevilacqua, L., Hagopian, K., 16. De Bary, A. (1879) in Vortrag auf der Versammlung (2004) Mitigation Adapt. Strategies Global Change Weindruch, R. & Ramsey, J. J. (2004) Acta der Naturforscher und Artze zu Cassel, ed. Trubner, Physiol. Scand. 182, 321–331. K. J. (Strassburg, Germany), pp. 1–30. 9, 261–272. 8. Chen, C. & Dickman, M. B. (2005) Proc. Natl. 17. Hertig, M., Taliaferro, W. H. & Schwartz, B. 24. Redman, R. S., Sheehan, K. B., Stout, R. G., Acad. Sci. USA 102, 3459–3464. (1937) J. Parasitol. 23, 326–329. Rodriguez, R. J. & Henson, J. M. (2002) Science 9. Bright, J. N. & Sansom, M. S. P. (2002) J. Phys. 18. Petrini, O. (1986) in Microbiology of the Phyllo- 298, 1581. Chem. B. 107, 627–636. sphere, eds. Fokkema, N. J. & van den Heuvel, J. 25. Redman, R. S., Freeman, S., Clifton, D. R., Mor- 10. Van Bel, A. J. E. & Gaupels, F. (2004) Mol. Plant (Cambridge Univ. Press, Cambridge, U.K.), pp. rel, J., Brown, G. & Rodriguez, R. J. (1999) Plant Pathol. 5, 495–504. 175–187. Physiol. 119, 795–804.

3176 ͉ www.pnas.org͞cgi͞doi͞10.1073͞pnas.0500367102 Rodriquez and Redman Downloaded by guest on October 2, 2021