REVIEW ARTICLE published: 28 November 2013 doi: 10.3389/fpls.2013.00460 Dissecting the integrative antioxidant and redox systems in plant mitochondria. Effect of stress and S-nitrosylation Juan J. Lázaro 1, Ana Jiménez 2 , Daymi Camejo 2 , Iván Iglesias-Baena 1, María del Carmen Martí 2†, Alfonso Lázaro-Payo 1, Sergio Barranco-Medina 1† and Francisca Sevilla 2 * 1 Department of Biochemistry and Cellular and Molecular Biology of Plants, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas, Granada, Spain 2 Department of Stress Biology and Plant Pathology, Centro de Edafología y Biología Aplicada del Segura, Consejo Superior de Investigaciones Científicas, Murcia, Spain Edited by: Mitochondrial respiration provides the energy needed to drive metabolic and transport Jose A. Traverso, Consejo Superior de processes in cells. Mitochondria are a significant site of reactive oxygen species (ROS) Investigaciones Científicas, Spain production in plant cells, and redox-system components obey fine regulation mechanisms Reviewed by: that are essential in protecting the mitochondrial integrity. In addition to ROS, there are Christine Helen Foyer, University of Leeds, UK compelling indications that nitric oxide can be generated in this organelle by both reductive Toru Hisabori, Tokyo Institute of and oxidative pathways. ROS and reactive nitrogen species play a key role in signaling Technology, Japan but they can also be deleterious via oxidation of macromolecules. The high production of *Correspondence: ROS obligates mitochondria to be provided with a set of ROS scavenging mechanisms. Francisca Sevilla, Department of The first line of mitochondrial antioxidants is composed of superoxide dismutase and the Stress Biology and Plant Pathology, Centro de Edafología y Biología enzymes of the ascorbate-glutathione cycle, which are not only able to scavenge ROS Aplicada del Segura, Consejo Superior but also to repair cell damage and possibly serve as redox sensors. The dithiol-disulfide de Investigaciones Científicas, exchanges form independent signaling nodes and act as antioxidant defense mechanisms Campus Universitario de Espinardo, E-30100 Murcia, Spain as well as sensor proteins modulating redox signaling during development and stress e-mail: [email protected] adaptation. The presence of thioredoxin (Trx), peroxiredoxin (Prx) and sulfiredoxin (Srx) in †Present address: the mitochondria has been recently reported. Cumulative results obtained from studies in Sergio Barranco-Medina, Department salt stress models have demonstrated that these redox proteins play a significant role in the of Biochemistry and Molecular establishment of salt tolerance.TheTrx/Prx/Srx system may be subjected to a fine regulated Biology, Saint Louis University, St. Louis, MO, USA; María del Carmen mechanism involving post-translational modifications, among which S-glutathionylation and Martí, Department of Plant Sciences, S-nitrosylation seem to exhibit a critical role that is just beginning to be understood. This University of Cambridge, Cambridge, review summarizes our current knowledge in antioxidative systems in plant mitochondria, UK their interrelationships, mechanisms of compensation and some unresolved questions, with special focus on their response to abiotic stress. Keywords: abiotic stress, ascorbate-glutathione cycle, mitochondria, peroxiredoxin, signaling, S-nitrosylation, sulfiredoxin, thioredoxin INTRODUCTION ROS in many other cellular processes, including its proposed role Plant mitochondria host some of the most important biologi- as signaling molecules under oxidative conditions (Dat et al., 2000; cal processes, i.e, oxidative phosphorylation, citric acid cycle and Mittler et al., 2011). The condition of signaling molecules implies fatty acid oxidation. Based on their physiological relevance, mito- a tight control of ROS-antioxidants’ interplay in the different cell chondria are involved in underpinning cellular proliferation, plant compartments, and the activation of signaling pathways by ROS growth, development and death (Millar et al., 2011). Although responsive regulatory genes has been suggested as contributing chloroplasts and peroxisomes are the major ROS producers in to plant tolerance toward different stresses (Schwarzländer and plant cells under light periods (Foyer and Noctor, 2003), mito- Finkemeier, 2013). Therefore, the response of plants to ROS is chondrial metabolism significantly accounts for the total ROS dose dependent (Veal et al., 2007). Under stress conditions, the generation (Noctor et al., 2007). Overall, complexes I and III of the presence of ROS is not always a symptom of cellular dysfunction, electron transport chain (ETC) are the main sites of ROS produc- but rather a signal to modulate transduction pathways through tion and about 1–5% of the total consumed oxygen is converted mitogen-activated protein kinases (MAPK) and transcription fac- into hydrogen peroxide (H2O2; Moller, 2001). tors (Jaspers and Kangasjärvi, 2010). In mammals, this signaling Initially, mitochondrial ROS were considered as an undesirable process is present in several diseases and shows the crosstalk by product with deleterious effects. Higher ROS amounts resulting between multiple transcription factors and the redox-regulating from uncontrolled ROS generation can cause oxidative stress by protein Trx (Burke-Gaffney et al., 2005). In plants, a much less damaging cellular components and affecting organelle integrity. A studied system, the involvement of Trx in redox signaling is being growing number of publications now recognize the implication of considered (Zaffagnini et al., 2012b). www.frontiersin.org November 2013 | Volume 4 | Article 460 | 1 “fpls-04-00460” — 2013/11/28 — 12:54 — page1—#1 Lázaro et al. Mitochondrial antioxidant and redox systems Besides ROS, plant mitochondria have also emerged as an of nuclear encoding, is increased during ETC inhibition by mito- important site for nitric oxide production by two main path- chondria to nucleus signaling (Van Aken et al., 2009a; Hartl and ways: a mitochondrial nitrite reducing activity whose site of NO• Finkemeier, 2012; Leister, 2012). In this process, organellar redox generation remains uncertain (Planchet et al., 2005), and the oxi- state and ROS metabolism have been poproposed as sources for dation of L-arginine by an elusive nitric oxide synthase (NOS; retrograde signals which could trigger gene expression responses Guo and Crawford, 2005). Formation of ROS in junction with and provide a metabolic flexibility which, during stress conditions, NO• may present a danger in the mitochondria. To maintain play an important role in the acclimation of plants (Rhoads and the cellular redox homeostasis and avoid an oxidative stress that Subbaiah, 2007; Woodson and Chory, 2008) could cause molecular damage, plant mitochondria possess a set of antioxidant enzymes such as manganese superoxide dismu- ROS PRODUCTION tase (Mn-SOD), enzymes of the ascorbate-glutathione cycle and A key feature of mitochondrial biochemistry is the unavoidable enzymes of the Trx/Prx/Srx system (Sevilla et al., 1982; Jiménez production of ROS, with complex I and complex III being the et al., 1997; Barranco-Medina et al., 2008b). These antioxidant major sites (Noctor et al., 2007). Under specific conditions ROS scavengers respond to the stress situations (Martí et al., 2011)by may be produced at complex II site, in the course of reverse regulating the level of ROS and modulating the redox signaling. electron transport (Turrens, 2003). ROS production is enhanced Along with ROS,reactive nitrogen species (RNS) are critical fac- under conditions of high matrix NADH+/NAD. On the other tors in signaling, by working as second messengers. The signaling hand, increased membrane potential correlates with more highly process can be indirectly exerted by molecules that have suffered reduced ETC components, so raising the probability of single elec- •− the oxidative damage by a reversible change in the redox state. Post- tron leak to oxygen and of O2 . This superoxide can, in turn, act translational modifications (PTMs) of redox cysteine residues of as substrate for the generation of secondary ROS such as H2O2 targets proteins constitute a secondary mitochondrial retrograde and hydroxyl radical (•OH). The magnitude of membrane poten- regulation (MRR) and can modulate ROS and RNS signaling tial is dependent on the activity of the energy-dissipating systems, (Hartl and Finkemeier, 2012). Among them, S-glutathionylation and on the oxidative phosphorylation. Hence, when ADP is being and S-nitrosylation have emerged as novel regulators in cell sig- actively phosphorylated, membrane potential and ROS are lower naling and response to stress conditions (Zaffagnini et al., 2012a; than when ADP is limiting. Increased energy dissipation can sim- Camejo et al., 2013a). Protein oligomerization and reversible ilarly be achieved by artificial uncouplers, uncoupling proteins overoxidation of cysteine residues add a further step into the (UCPs; Moller, 2001; Finkel, 2011; Collins et al., 2012) and by redox regulation (Barranco-Medina et al., 2009; Iglesias-Baena the plant mitochondria potassium channel (PmitoKATP ) which et al., 2010). can be stress-activated through several mechanisms, including In this work we dissect the different aspects of the redox activation by ROS, so indicating the fine regulation of this bio- regulation of plant mitochondria, with special emphasis on the chemical pathway. Dissipation of membrane potential directly