Antioxidative enzymes from chloroplasts, mitochondria, and peroxisomes during leaf senescence of nodulated pea plants

In this work the influence of the nodulation of pea (Pisum sativum L.) plants on the oxidative metabolism of different leaf organelles from young and senescent plants was studied. Chloroplasts, mitochondria, and peroxisomes were purified from leaves of nitrate-fed and Rhizobium leguminosarum-nodulated pea plants at two developmental stages (young and senescent plants). In these cell organelles, the activity of the ascorbate-glutathione cycle enzymes ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and glutathione reductase (GR), and the ascorbate and glutathione contents were determined. In addition, the total superoxide dismutase (SOD) activity, the pattern of mitochondrial and peroxisomal NADPH-generating dehydrogenases, some of the peroxisomal photorespiratory enzymes, the glyoxylate cycle and oxidative metabolism enzymes were also analysed in these organelles. Results obtained on the metabolism of cell organelles indicate that nodulation with Rhizobium accelerates senescence in pea leaves. A considerable decrease of the ascorbate content of chloroplasts, mitochondria, and peroxisomes was found, and in these conditions a metabolic conversion of leaf peroxisomes into glyoxysomes, characteristic of leaf senescence, took place.     

植物过氧化物酶体在活性氧信号网络中的作用

过氧化物酶体是高度动态、代谢活跃的细胞器,主要参与脂肪酸等脂质的代谢及产生和清除不同的活性氧(reactive oxygen species, ROS)。ROS是细胞有氧代谢的副产物。当胁迫长期作用于植物,过量的ROS会引起氧胁迫,损害细胞结构和功能的完整性,导致细胞代谢减缓,活性降低,甚至死亡;但低浓度的ROS则作为分子信号,感应细胞ROS/氧化还原变化,从而触发由环境因素导致的过氧化物酶体动力学以及依赖ROS信号网络改变而产生快速、特异性的应答。ROS也可以通过直接或间接调节细胞生长来控制植物的发育,是植物发育的重要调节剂。此外,过氧化物酶体的动态平衡由ROS、过氧化物酶体蛋白酶及自噬过程调节,对于维持细胞的氧化还原平衡至关重要。本文就过氧化物酶体中ROS的产生和抗氧化剂的调控机制进行综述,以期为过氧化物酶体如何感知环境变化,以及在细胞应答中,ROS作为重要信号分子的研究提供参考。     

Deconvoluting the role of reactive oxygen species and autophagy in human diseases

Reactive oxygen species (ROS), chemically reactive molecules containing oxygen, can form as a natural byproduct of the normal metabolism of oxygen and also have their crucial roles in cell homeostasis. Of note, the major intracellular sources including mitochondria, endoplasmic reticulum (ER), peroxisomes and the NADPH oxidase (NOX) complex have been identified in cell membranes to produce ROS. Interestingly, autophagy, an evolutionarily conserved lysosomal degradation process in which a cell degrades long-lived proteins and damaged organelles, has recently been well-characterized to be regulated by different types of ROS. Accumulating evidence has demonstrated that ROS-modulated autophagy has numerous links to a number of pathological processes, including cancer, ageing, neurodegenerative diseases, type-II diabetes, cardiovascular diseases, muscular disorders, hepatic encephalopathy and immunity diseases. In this review, we focus on summarizing the molecular mechanisms of ROS-regulated autophagy and their relevance to diverse diseases, which would shed new light on more ROS modulators as potential therapeutic drugs for fighting human diseases.     

An Arabidopsis dynamin-related protein, DRP3A, controls both peroxisomal and mitochondrial division

Peroxisomes undergo dramatic changes in size, shape, number, and position within the cell, but the division process of peroxisomes has not been characterized. We screened a number of Arabidopsis mutants with aberrant peroxisome morphology (apm mutants). In one of these mutants, apm1, the peroxisomes are long and reduced in number, apparently as a result of inhibition of division. We showed that APM1 encodes dynamin-related protein 3A (DRP3A), and that mutations in APM1/DRP3A also caused aberrant morphology of mitochondria. The transient expression analysis showed that DRP3A is associated with the cytosolic side of peroxisomes. These findings indicate that the same dynamin molecule is involved in peroxisomal and mitochondrial division in higher plants. We also report that the growth of Arabidopsis, which requires the cooperation of various organelles, including peroxisomes and mitochondria, is repressed in apm1, indicating that the changes of morphology of peroxisomes and mitochondria reduce the efficiency of metabolism in these organelles.     

Cellular oxidation of lignoceric acid is regulated by the subcellular localization of lignoceroyl-CoA ligases

The acyl-CoA ligases convert free fatty acids to acyl-CoA derivatives, and these enzymes have been shown to be present in mitochondria, peroxisomes, and endoplasmic reticulum. Because their activity is obligatory for fatty acid metabolism, it is important to identify their substrate specificities and subcellular distributions to further understand the cellular regulation of these pathways. To define the role of the enzymes and organelles involved in the metabolism of very long chain (VLC) fatty acids, we studied human genetic cell mutants impaired for the metabolism of these molecules. Fibroblast cell lines were derived from patients with X-linked adrenoleukodystrophy (X-ALD) and Zellweger's cerebro-hepato-renal syndrome (CHRS). While peroxisomes are present and morphologically normal in X-ALD, they are either greatly reduced in number or absent in CHRS. Palmitoyl-CoA ligase is known to be present in mitochondria, peroxisomes, and endoplasmic reticulum (microsomes). We found enzyme-dependent formation of lignoceroyl-CoA in these same organelles (specific activities were 0.32 +/- 0.12, 0.86 +/- 0.12, and 0.78 +/- 0.07 nmol/h per mg protein, respectively). However, lignoceroyl-CoA synthesis was inhibited by an antibody to palmitoyl-CoA ligase in isolated mitochondria while it was not inhibited in peroxisomes or endoplasmic reticulum (ER). This suggests that palmitoyl-CoA ligase and lignoceroyl-CoA are different enzymes and that mitochondria lack lignoceroyl-CoA ligase. This conclusion is further supported by data showing that oxidation of lignoceric acid was found almost exclusively in peroxisomes (0.17 nmol/h per mg protein) but was largely absent from mitochondria and the finding that monolayers of CHRS fibroblasts lacking peroxisomes showed a pronounced deficiency in lignoceric acid oxidation in situ (1.8% of control). In spite of the observation that lignoceroyl-CoA ligase activity is present on the cytoplasmic surface of ER, our data indicate that lignoceroyl-CoA synthesized by ER is not available for oxidation in mitochondria. This organelle plays no physiological role in the beta-oxidation of VLC fatty acids. Furthermore, the normal peroxisomal oxidation of lignoceroyl-CoA but deficient oxidation of lignoceric acid in X-ALD cells indicates that cellular VLC fatty acid oxidation is dependent on peroxisomal lignoceroyl-CoA ligase. These studies allow us to propose a model for the subcellular localization of various acyl-CoA ligases and to describe how these enzymes control cellular fatty acid metabolism.     

Beneficial interactions of mitochondrial metabolism with photosynthetic carbon assimilation

Chloroplasts and mitochondria are traditionally considered to be autonomous organelles but they are not as independent as they were once thought to be. Mitochondrial metabolism, particularly the bioenergetic reactions of oxidative electron transport and phosphorylation, continue to be active in the light and are essential for sustaining photosynthetic carbon assimilation. The marked and mutually beneficial interaction between mitochondria and chloroplasts is intriguing. The key compartments within plant cells, including not only mitochondria and chloroplasts but also the peroxisomes and cytosol, appear to be in a delicate metabolic equilibrium. Disturbance of any of these compartments perturbs the metabolism of whole cell. Nevertheless, mitochondria appear to be the key players because they function during both photorespiration and dark respiration.     

Plant peroxisomes at the crossroad of NO and H_2O_2 metabolism

Plant peroxisomes are subcellular compartments involved in many biochemical pathways during the life cycle of a plant but also in the mechanism of response against adverse environmental conditions. These organelles have an active nitro-oxidative metabolism under physiological conditions but this could be exacerbated under stress situations. Furthermore, peroxisomes have the capacity to proliferateand also undergo biochemical adaptations depending on the surrounding cellular status. An important characteristic of peroxisomes is that they have a dynamic metabolism of reactive nitrogen and oxygen species(RNS and ROS) which generates two key molecules, nitric oxide(NO) and hydrogen peroxide(H_2O_2). These molecules can exert signaling functions by means of post-translational modifications that affect the functionality of target molecules like proteins, peptides or fatty acids. This review provides an overview of the endogenous metabolism of ROS and RNS in peroxisomes with special emphasis on polyamine and uric acid metabolism as well as the possibility that these organelles could be a source of signal molecules involved in the functional interconnection with other subcellular compartments.     

Mitochondria are the main target for oxidative damage in leaves of wheat (Triticum aestivum L.)

Photosynthesis, respiration, and other processes produce reactive oxygen species (ROS) that can cause oxidative modifications to proteins, lipids, and DNA. The production of ROS increases under stress conditions, causing oxidative damage and impairment of normal metabolism. In this work, oxidative damage to various subcellular compartments (i.e. chloroplasts, mitochondria, and peroxisomes) was studied in two cultivars of wheat differing in ascorbic acid content, and growing under good irrigation or drought. In well-watered plants, mitochondria contained 9-28-fold higher concentrations of oxidatively modified proteins than chloroplasts or peroxisomes. In general, oxidative damage to proteins was more intense in the cultivar with the lower content of ascorbic acid, particularly in the chloroplast stroma. Water stress caused a marked increase in oxidative damage to proteins, particularly in mitochondria and peroxisomes. These results indicate that mitochondria are the main target for oxidative damage to proteins under well-irrigated and drought conditions.     

Bodipy-C12在癌细胞过氧化物酶体中富集

目的:研究并比较Bodipy标记的月桂酸(Bodipy-C12)在癌细胞与正常细胞中的亚细胞定位。方法:在多种癌细胞和正常细胞的培养基中加入Bodipy-C12(1μg/m L),利用共聚焦显微镜活细胞定时间隔拍摄,结合不同细胞器的分子标记蛋白,观察Bodipy-C12五分钟内在不同细胞器中的定位。结果:在人肝癌细胞系HepG2细胞中,Bodpy-C12信号不仅仅存在于线粒体和脂滴,同时富集于过氧化物酶体中。我们分别采用Pex3-GFP、Pex14-GFP、GFP-Pex16、GFP-SKL和GFP-Pmp34等特异性定位的过氧化物酶体蛋白,确认Bodpy-C12信号富集于过氧化物酶体。此外,过氧化物酶体中Bodpy-C12信号的富集发生在更多的癌细胞系中,例如结肠癌细胞HCT116和乳腺癌细胞MCF7。不同的是,在正常细胞系如3T3-L1,NRK和COS7中,Bodipy-C12信号存在于线粒体和脂滴中,但未在过氧化物酶体中检测到。结论:Bodipy-C12信号存在于正常细胞和癌细胞的脂滴和线粒体中,且其在癌细胞过氧化物酶体中富集,而不存在于正常细胞的过氧化物酶体中,预示癌细胞中过氧化物酶体脂代谢的差异。     

The peroxisomal Lon protease LonP2 in aging and disease: functions and comparisons with mitochondrial Lon protease LonP1

Peroxisomes are ubiquitous eukaryotic organelles with the primary role of breaking down very long‐ and branched‐chain fatty acids for subsequent β‐oxidation in the mitochondrion. Like mitochondria, peroxisomes are major sites for oxygen utilization and potential contributors to cellular oxidative stress. The accumulation of oxidatively damaged proteins, which often develop into inclusion bodies (of oxidized, aggregated, and cross‐linked proteins) within both mitochondria and peroxisomes, results in loss of organelle function that may contribute to the aging process. Both organelles possess an isoform of the Lon protease that is responsible for degrading proteins damaged by oxidation. While the importance of mitochondrial Lon (LonP1) in relation to oxidative stress and aging has been established, little is known regarding the role of LonP2 and aging‐related changes in the peroxisome. Recently, peroxisome dysfunction has been associated with aging‐related diseases indicating that peroxisome maintenance is a critical component of ‘healthy aging’. Although mitochondria and peroxisomes are both needed for fatty acid metabolism, little work has focused on understanding the relationship between these two organelles including how age‐dependent changes in one organelle may be detrimental for the other. Herein, we summarize findings that establish proteolytic degradation of damaged proteins by the Lon protease as a vital mechanism to maintain protein homeostasis within the peroxisome. Due to the metabolic coordination between peroxisomes and mitochondria, understanding the role of Lon in the aging peroxisome may help to elucidate cellular causes for both peroxisome and mitochondrial dysfunction.     

Peroxisomes sense and respond to environmental cues by regulating ROS and RNS signalling networks

Background Peroxisomes are highly dynamic, metabolically active organelles that used to be regarded as a sink for H₂O₂ generated in different organelles. However, peroxisomes are now considered to have a more complex function, containing different metabolic pathways, and they are an important source of reactive oxygen species (ROS), nitric oxide (NO) and reactive nitrogen species (RNS). Over-accumulation of ROS and RNS can give rise oxidative and nitrosative stress, but when produced at low concentrations they can act as signalling molecules.Scope This review focuses on the production of ROS and RNS in peroxisomes and their regulation by antioxidants. ROS production is associated with metabolic pathways such as photorespiration and fatty acid β-oxidation, and disturbances in any of these processes can be perceived by the cell as an alarm that triggers defence responses. Genetic and pharmacological studies have shown that photorespiratory H₂O₂ can affect nuclear gene expression, regulating the response to pathogen infection and light intensity. Proteomic studies have shown that peroxisomal proteins are targets for oxidative modification, S-nitrosylation and nitration and have highlighted the importance of these modifications in regulating peroxisomal metabolism and signalling networks. The morphology, size, number and speed of movement of peroxisomes can also change in response to oxidative stress, meaning that an ROS/redox receptor is required. Information available on the production and detection of NO/RNS in peroxisomes is more limited. Peroxisomal homeostasis is critical for maintaining the cellular redox balance and is regulated by ROS, peroxisomal proteases and autophagic processes.Conclusions Peroxisomes play a key role in many aspects of plant development and acclimation to stress conditions. These organelles can sense ROS/redox changes in the cell and thus trigger rapid and specific responses to environmental cues involving changes in peroxisomal dynamics as well as ROS- and NO-dependent signalling networks, although the mechanisms involved have not yet been established. Peroxisomes can therefore be regarded as a highly important decision-making platform in the cell, where ROS and RNS play a determining role.     

Organic anion transporters,OAT1 and OAT3, are crucial biopterin transporters involved in bodily distribution of tetrahydrobiopterin and exclusion of its excess

Like mitochondria, peroxisomes produce reactive oxygen species (ROS), compounds which have been implicated to play an important role in many degenerative diseases and aging itself, and an exaggerated ROS production might occur in altered or older organelles. Growing evidence shows that autophagy, a required function in cell housekeeping during fasting, can remove damaged macromolecules, organelles, and membranes selectively. Proliferation of peroxisomes can be enhanced in liver cells by perfluorooctanoic acid (PFOA), which causes a marked increase of the Acyl-CoA oxidase (ACOX) activity and no significant change in urate oxidase (UOX) activity. The administration of antilipolytic drugs to fasted animals was shown to intensify autophagy. Here we tested the hypothesis that autophagy may distinguish and remove older from younger peroxisomes in rat liver. Male Sprague-Dawley rats were given PFOA (150 mg/kg body weight) or vehicle. Animals were sacrificed at different times following PFOA administration, and 3 h after the induction of autophagy with the antilipolytic agent 3,5-dimethyl pyrazole (DMP, 12 mg/kg body weight). The levels of ACOX and UOX activity were measured in the liver tissue. Results showed that autophagy caused a parallel, significant decrease in both enzymes activity in control rats, and that in PFOA-treated rats the effects were different and changed with PFOA time administration. Changes are compatible with the hypothesis that newly formed ACOX-rich peroxisomes are resistant to pexophagy and that sensitivity to pexophagy increases with increasing peroxisomal “age.” In conclusion, there is indirect evidence supporting the hypothesis that autophagy may recognize and degrade older peroxisomes.     

Reactive oxygen species, antioxidant systems and nitric oxide in peroxisomes

Peroxisomes are subcellular organelles with an essentially oxidative type of metabolism. Like chloroplasts and mitochondria, plant peroxisomes also produce superoxide radicals (O2*(-)) and there are, at least, two sites of superoxide generation: one in the organelle matrix, the generating system being xanthine oxidase, and another site in the peroxisomal membranes dependent on NAD(P)H. In peroxisomal membranes, three integral polypeptides (PMPs) with molecular masses of 18, 29 and 32 kDa have been shown to generate radicals O2*(-). Besides catalase, several antioxidative systems have been demonstrated in plant peroxisomes, including different superoxide dismutases, the ascorbate-glutathione cycle, and three NADP-dependent dehydrogenases. A CuZn-SOD and two Mn-SODs have been purified and characterized from different types of peroxisomes. The four enzymes of the ascorbate-glutathione cycle (ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase, and glutathione reductase) as well as the antioxidants glutathione and ascorbate have been found in plant peroxisomes. The recycling of NADPH from NADP(+) can be carried out in peroxisomes by three dehydrogenases: glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and isocitrate dehydrogenase. In the last decade, different experimental evidence has suggested the existence of cellular functions for peroxisomes related to reactive oxygen species (ROS), but the recent demonstration of the presence of nitric oxide synthase (NOS) in plant peroxisomes implies that these organelles could also have a function in plant cells as a source of signal molecules like nitric oxide (NO*), superoxide radicals, hydrogen peroxide, and possibly S-nitrosoglutathione (GSNO).     

Plastid-nuclear complexes in the photosynthesizing cells from their mitosis up to programmed death

Permanent plastid-nuclear complexes (PNCs) exist in tobacco cells from their mitosis up to programmed cell death (PCD). PNCs in senescing cells of tobacco leaves were typical by enclosure of peroxisomes and mitochondria among chloroplasts which were in contact with nucleus. Such a complex position provides simultaneous interaction of these organelles and direct regulation of metabolism and PCD avoiding the cytosol.     

Immunological evidence for the presence of peroxiredoxin in pea leaf peroxisomes and response to oxidative stress conditions

Peroxiredoxins (Prxs) constitute a group of thiol-specific antioxidant enzymes which are present in bacteria, yeasts, and in plant and animal cells. Although Prxs are mainly localized in the cytosol, they are also present in mitochondria, chloroplasts, and nuclei, but there is no evidence of the existence of Prxs in plant peroxisomes. Using soluble fractions (matrices) of peroxisomes purified from leaves of pea (Pisum sativum L.) plants, the immunological analysis with affinity-purified IgG against yeast Prx1 revealed the presence of an immunoreactive band of about 50 kDa. The apparent molecular mass of the peroxisomal Prx was not sensitive to oxidizing and reducing conditions what could be a mechanism of protection against the oxidative environment existing in peroxisomes. Postembedment, EM immunocytochemical analysis with affinity-purified IgG against yeast Prx1 antibodies, confirmed that this protein was present in the peroxisomal matrix, mitochondria, and chloroplasts. In pea plants grown under oxidative stress conditions, the protein level of peroxisomal Prx was differentially modulated, being slightly induced by growth of plants with 50 µM CdCl₂, but being significantly reduced by treatment with the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). The presence in the matrix of peroxisomes of a protein immunorelated to Prx of about 50 kDa, which is in the range of molecular mass of the dimeric form of other Prxs, opens new questions on the molecular properties of Prxs, but also on their function in the metabolism of reactive oxygen and nitrogen species (ROS/RNS) in these plant cell organelles, where they could be involved in the regulation of hydrogen peroxide and/or peroxynitrite.     

Induction and subcellular localization of enzymes participating in propionate metabolism in Candida tropicalis

Candida tropicalis, a representative alkane- and higher fatty acid-utilizing yeast, can grow on propionate used as sole carbon and energy source. Initial pH of the medium markedly affected the growth of the yeast on propionate. In propionate-grown cells, several enzymes associated with peroxisomes and/or participating in propionate metabolism were induced in connection with the appearance of the characteristic peroxisomes. Acetate-grown cells of this yeast had only few peroxisomes, while alkane-grown cells contained conspicuous numbers of the organelles. As compared with alkane-grown cells, some specific features were observed in peroxisomes and enzymes associated with the organelles of propionate-grown cells: The shape of peroxisomes was large but the number was small; unlike localization of catalase in peroxisomes of alkane-grown cells, the enzyme of propionate-grown cells was mainly localized in cytoplasm; as for carnitine acetyltransferase localized almost equally in peroxisomes and mitochondria in alkane-grown cells, propionate-grown cells contained mainly the mitochondrial type enzyme. A propionate-activating enzyme, which was different from acetyl-CoA synthetase, was also induced in cytoplasm of propionate-grown cells. The role of carnitine acetyltransferase and the propionate-activating enzyme in propionate metabolism is discussed in comparison with the role of carnitine acetyltransferase and acetyl-CoA synthetase in acetate metabolism.     

Physiology of pepper fruit and the metabolism of antioxidants: chloroplasts,mitochondria and peroxisomes

Background and Aims Pepper (Capsicum annuum) contains high levels of antioxidants, such as vitamins A and C and flavonoids. However, information on the role of these beneficial compounds in the physiology of pepper fruit remains scarce. Recent studies have shown that antioxidants in ripe pepper fruit play a key role in responses to temperature changes, and the redox state at the time of harvest affects the nutritional value for human consumption. In this paper, the role of antioxidant metabolism of pepper fruit during ripening and in the response to low temperature is addressed, paying particular attention to ascorbate, NADPH and the superoxide dismutase enzymatic system. The participation of chloroplasts, mitochondria and peroxisomes in the ripening process is also investigated.Scope and Results Important changes occur at a subcellular level during ripening of pepper fruit. Chloroplasts turn into chromoplasts, with drastic conversion of their metabolism, and the role of the ascorbate–glutathione cycle is essential. In mitochondria from red fruits, higher ascorbate peroxidase (APX) and Mn-SOD activities are involved in avoiding the accumulation of reactive oxygen species in these organelles during ripening. Peroxisomes, whose antioxidant capacity at fruit ripening is substantially affected, display an atypical metabolic pattern during this physiological stage. In spite of these differences observed in the antioxidative metabolism of mitochondria and peroxisomes, proteomic analysis of these organelles, carried out by 2-D electrophoresis and MALDI-TOF/TOF and provided here for the first time, reveals no changes between the antioxidant metabolism from immature (green) and ripe (red) fruits.Conclusions Taken together, the results show that investigation of molecular and enzymatic antioxidants from cell compartments, especially chloroplasts, mitochondria and peroxisomes, is a useful tool to study the physiology of pepper fruit, particularly in the context of expanding their shelf-life after harvest and in maintaining their nutritional value.     

Optimization of photosynthesis by multiple metabolic pathways involving interorganelle interactions: resource sharing and ROS maintenance as the bases

The bioenergetic processes of photosynthesis and respiration are mutually beneficial. Their interaction extends to photorespiration, which is linked to optimize photosynthesis. The interplay of these three pathways is facilitated by two major phenomena: sharing of energy/metabolite resources and maintenance of optimal levels of reactive oxygen species (ROS). The resource sharing among different compartments of plant cells is based on the production/utilization of reducing equivalents (NADPH, NADH) and ATP as well as on the metabolite exchange. The responsibility of generating the cellular requirements of ATP and NAD(P)H is mostly by the chloroplasts and mitochondria. In turn, besides the chloroplasts, the mitochondria, cytosol and peroxisomes are common sinks for reduced equivalents. Transporters located in membranes ensure the coordinated movement of metabolites across the cellular compartments. The present review emphasizes the beneficial interactions among photosynthesis, dark respiration and photorespiration, in relation to metabolism of C, N and S. Since the bioenergetic reactions tend to generate ROS, the cells modulate chloroplast and mitochondrial reactions, so as to ensure that the ROS levels do not rise to toxic levels. The patterns of minimization of ROS production and scavenging of excess ROS in intracellular compartments are highlighted. Some of the emerging developments are pointed out, such as model plants, orientation/movement of organelles and metabolomics.     

Plant peroxisomes as a source of signalling molecules

Peroxisomes are pleiomorphic, metabolically plastic organelles. Their essentially oxidative function led to the adoption of the name 'peroxisome'. The dynamic and diverse nature of peroxisome metabolism has led to the realisation that peroxisomes are an important source of signalling molecules that can function to integrate cellular activity and multicellular development. In plants defence against predators and a hostile environment is of necessity a metabolic and developmental response--a plant has no place to hide. Mutant screens are implicating peroxisomes in disease resistance and signalling in response to light. Characterisation of mutants disrupted in peroxisomal beta-oxidation has led to a growing appreciation of the importance of this pathway in the production of jasmonic acid, conversion of indole butyric acid to indole acetic acid and possibly in the production of other signalling molecules. Likewise the role of peroxisomes in the production and detoxification of reactive oxygen, and possibly reactive nitrogen species and changes in redox status, suggests considerable scope for peroxisomes to contribute to perception and response to a wide range of biotic and abiotic stresses. Whereas the peroxisome is the sole site of beta-oxidation in plants, the production and detoxification of ROS in many cell compartments makes the specific contribution of the peroxisome much more difficult to establish. However progress in identifying peroxisome specific isoforms of enzymes associated with ROS metabolism should allow a more definitive assessment of these contributions in the future.     

Mitochondria are targets for peroxisome-derived oxidative stress in cultured mammalian cells

Many cellular processes are driven by spatially and temporally regulated redox-dependent signaling events. Although mounting evidence indicates that organelles such as the endoplasmic reticulum and mitochondria can function as signaling platforms for oxidative stress-regulated pathways, little is known about the role of peroxisomes in these processes. In this study, we employ targeted variants of the genetically encoded photosensitizer KillerRed to gain a better insight into the interplay between peroxisomes and cellular oxidative stress. We show that the phototoxic effects of peroxisomal KillerRed induce mitochondria-mediated cell death and that this process can be counteracted by targeted overexpression of a select set of antioxidant enzymes, including peroxisomal glutathione S-transferase kappa 1, superoxide dismutase 1, and mitochondrial catalase. We also present evidence that peroxisomal disease cell lines deficient in plasmalogen biosynthesis or peroxisome assembly are more sensitive to KillerRed-induced oxidative stress than control cells. Collectively, these findings confirm and extend previous observations suggesting that disturbances in peroxisomal redox control and metabolism can sensitize cells to oxidative stress. In addition, they lend strong support to the ideas that peroxisomes and mitochondria share a redox-sensitive relationship and that the redox communication between these organelles is not only mediated by diffusion of reactive oxygen species from one compartment to the other. Finally, these findings indicate that mitochondria may act as dynamic receivers, integrators, and transmitters of peroxisome-derived mediators of oxidative stress, and this may have profound implications for our views on cellular aging and age-related diseases.