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Antioxidant homeostasis

Antioxidant homeostasis

Reed, W. Antioxudant Cell Antioxidant homeostasis homeosttasis : — In particular, diurnal Antioxidant homeostasis of alternative oxidase expression are lost, the relative importance of the different catalase isoforms is modified, and the transcripts, protein, and activity of cytosolic ascorbate peroxidase are enhanced markedly. Antioxidant homeostasis

Antioxidant homeostasis -

Ali, R. Arch, C. Xiong, D. Wozniak, L. Aging 29 , Gao, K. Dong, A. Zhao, H. Wang, J. Nano Res. Zhou, J. Chen, X. Tian, L. Xiao, G. Yang Nanoscale 9 , Zhang, S.

Yin, W. He, W. Lu, M. Ma, N. Gu, Y. Zhang J. Zelko, T. Mariani, R. Filipovic, I. Ivanovic-Burmazovic, F. Beuerle, P. Witte, A. Jalilov, L. Nilewski, V.

Berka, C. Zhang, A. Yakovenko, G. Wu, T. ACS Nano 11 , Shen, W. Gao, Z. Lu, X. Korsvik, S. Patil, S. Seal, W. Heckert, A. Karakoti, S. Biomaterials 29 , Celardo, M. De Nicola, C. Mandoli, J.

Pedersen, E. Traversa, L. ACS Nano 5 , Singh, J. Dowding, S. Kim, T. Kim, I. Choi, M. Soh, D. Kim, Y. Kim, H. Jang, H. Park, S. Park, T. Yu, B. Yoon, S. Lee, T. Heckman, W. DeCoteau, A. Estevez, K. Reed, W. Costanzo, D. Sanford, J. Leiter, J. Clauss, K. Knapp, C. Gomez, P. Mullen, E.

Rathbun, K. Prime, J. Marini, J. Patchefsky, A. Patchefsky, R. Hailstone, J. ACS Nano 7 , Kwon, M. Cha, D. Kim, D.

Kim, M. Soh, K. Shin, T. Hyeon, I. ACS Nano 10 , Tarnuzzer, J. Colon, S. Nano Lett. Hirst, A. Karakoti, R. Tyler, N. Sriranganathan, S. Seal, C. Small 5 , Liu, W. Wei, Q. Yuan, X. Zhang, N. Du, G. Ma, C.

Yan, D. Zeng, Y. Li, X. Ge, Q. Guo, X. Lou, Z. Cao, B. Hu, N. Long, Y. Mao, C. Guan, M. Li, K. Dong, N. Gao, J. Ren, Y. Zheng, X. Biomaterials 98 , 92 Ragg, A. Schilmann, K. Korschelt, C. Wieseotte, M. Kluenker, M. Viel, L. Voelker, S. Preiss, J. Herzberger, H.

Frey, K. Heinze, P. Bluemler, M. Tahir, F. Natalio, W. B 4 , Mu, X. Zhao, J. Li, E. Yang, X. Guo, L. Sun, X. Chen, D.

Zorov, M. Juhaszova, S. Srinivasan, N. Fontanesi, I. Soto, D. Horn, A. Cell Physiol. Davis, S. Miller, C. Herrnstadt, S. Ghosh, E. Fahy, L. Shinobu, D. Galasko, L. Thal, M. Beal, N. Howell, W. Mutisya, A. Bowling, M. x Search in Google Scholar PubMed.

Zsurka, W. Lancet Neurol. Singh, G. Halliwell, J. Biochem J. Deisseroth, A. Góth, P. Rass, A. CNS Drugs 8 , Pirmohamed, J. Wasserman, E. Karakoti, J. King, S. Self, Chem. Kim, J. ACS Biomater. Zhang, Z. Wang, X.

Li, L. Wang, M. Yin, L. Wang, N. Chen, C. Fan, H. Gatenby, R. Cancer 8 , 56 Rockwell, I. Dobrucki, E. Kim, S. Marrison, V. Prasad, C. Gordijo, A. Abbasi, A. Maeda, A. Ip, A. Rauth, R. DaCosta, X. ACS Nano 8 , Fan, W. Bu, B. Shen, Q. He, Z. Cui, Y. Zheng, K. Cho, H.

Jeon, D. Kim, C. Song, N. Lee, S. Choi, T. Zhen, Y. Liu, L. Bai, X. Jia, H. Tian, X. Peng, M. Dong, B.

Ran, W. Hao, Q. Yang, L. Tan, K. Shi, Z. Interfaces 9 , Chen, J. ACS Nano 12 , Seeher, B. Carlson, A. Miniard, E. Wirth, Y. Mahdi, D. Cisplatin induces a mitochondrial-ROS response that contributes to cytotoxicity depending on mitochondrial redox status and bioenergetic functions.

PloS ONE ; 8 : e Article PubMed PubMed Central Google Scholar. Itoh T, Terazawa R, Kojima K, Nakane K, Deguchi T, Ando M et al.

Cisplatin induces production of reactive oxygen species via NADPH oxidase activation in human prostate cancer cells. Free Radic Res ; 45 : — Roh JL, Park JY, Kim EH, Jang HJ, Kwon M. Activation of mitochondrial oxidation by PDK2 inhibition reverses cisplatin resistance in head and neck cancer.

Cancer Lett ; : 20— Yang YJ, Baek JY, Goo J, Shin Y, Park JK, Jang JY et al. Effective killing of cancer cells through ros-mediated mechanisms by AMRI targeting peroxiredoxin I. Antioxid Redox Signal ; 24 : — Wason MS, Colon J, Das S, Seal S, Turkson J, Zhao J et al. Sensitization of pancreatic cancer cells to radiation by cerium oxide nanoparticle-induced ROS production.

Nanomedicine ; 9 : — Alajez NM, Shi W, Hui AB, Yue S, Ng R, Lo KW et al. Targeted depletion of BMI1 sensitizes tumor cells to Pmediated apoptosis in response to radiation therapy. Singh A, Bodas M, Wakabayashi N, Bunz F, Biswal S. Gain of Nrf2 function in non-small-cell lung cancer cells confers radioresistance.

Kim YS, Kang MJ, Cho YM. Low production of reactive oxygen species and high DNA repair: mechanism of radioresistance of prostate cancer stem cells. Anticancer Res ; 33 : — Ren D, Villeneuve NF, Jiang T, Wu T, Lau A, Toppin HA et al. Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism.

Fuchs-Tarlovsky V. Role of antioxidants in cancer therapy. Nutrition ; 29 : 15— Leon-Gonzalez AJ, Auger C, Schini-Kerth VB. Pro-oxidant activity of polyphenols and its implication on cancer chemoprevention and chemotherapy. Biochem Pharmacol ; 98 : — Filomeno M, Bosetti C, Bidoli E, Levi F, Serraino D, Montella M et al.

Mediterranean diet and risk of endometrial cancer: a pooled analysis of three Italian case-control studies. Br J Cancer ; : — Yan B, Stantic M, Zobalova R, Bezawork-Geleta A, Stapelberg M, Stursa J et al. Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner.

BMC Cancer ; 15 : Harris IS, Treloar AE, Inoue S, Sasaki M, Gorrini C, Lee KC et al. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Raj L, Ide T, Gurkar AU, Foley M, Schenone M, Li X et al.

Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Shaw AT, Winslow MM, Magendantz M, Ouyang C, Dowdle J, Subramanian A et al.

Selective killing of K-ras mutant cancer cells by small molecule inducers of oxidative stress. Dang CV. Links between metabolism and cancer. Genes Dev ; 26 : — Sainz RM, Lombo F, Mayo JC.

Radical decisions in cancer: redox control of cell growth and death. Cancers ; 4 : — Piskounova E, Agathocleous M, Murphy MM, Hu Z, Huddlestun SE, Zhao Z et al.

Oxidative stress inhibits distant metastasis by human melanoma cells. Fan J, Ye J, Kamphorst JJ, Shlomi T, Thompson CB, Rabinowitz JD. Quantitative flux analysis reveals folate-dependent NADPH production. Alberghina L, Gaglio D. Redox control of glutamine utilization in cancer. Jiang P, Du W, Wu M.

Regulation of the pentose phosphate pathway in cancer. Protein Cell ; 5 : — Currie E, Schulze A, Zechner R, Walther TC, Farese RV Jr.

Cellular fatty acid metabolism and cancer. Cell Metab ; 18 : — Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer ; 11 : 85— Vander Heiden MG, Cantley LC, Thompson CB.

Understanding the Warburg effect: the metabolic requirements of cell proliferation. Levine AJ, Puzio-Kuter AM. The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes.

Zhang D, Li J, Wang F, Hu J, Wang S, Sun Y. Cancer Lett ; : — Kroemer G, Pouyssegur J. Tumor cell metabolism: cancer's Achilles' heel. Cancer Cell ; 13 : — Zhai X, Yang Y, Wan J, Zhu R, Wu Y.

Oncology Rep ; 30 : — Article CAS Google Scholar. Zhang X, Fryknas M, Hernlund E, Fayad W, De Milito A, Olofsson MH et al. Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments.

Nat Commun ; 5 : Clem B, Telang S, Clem A, Yalcin A, Meier J, Simmons A et al. Small-molecule inhibition of 6-phosphofructokinase activity suppresses glycolytic flux and tumor growth.

Mol Cancer Ther ; 7 : — Chen J, Xie J, Jiang Z, Wang B, Wang Y, Hu X. Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2.

Oncogene ; 30 : — Godoy A, Ulloa V, Rodriguez F, Reinicke K, Yanez AJ, Garcia Mde L et al. Differential subcellular distribution of glucose transporters GLUT and GLUT9 in human cancer: ultrastructural localization of GLUT1 and GLUT5 in breast tumor tissues.

J Cell Physiol ; : — Aykin-Burns N, Ahmad IM, Zhu Y, Oberley LW, Spitz DR. Increased levels of superoxide and H2O2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation.

Biochem J ; : 29— Le A, Cooper CR, Gouw AM, Dinavahi R, Maitra A, Deck LM et al. Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Li J, Csibi A, Yang S, Hoffman GR, Li C, Zhang E et al. Synthetic lethality of combined glutaminase and Hsp90 inhibition in mTORC1-driven tumor cells.

Proc Natl Acad Sci USA ; : E21—E Carracedo A, Cantley LC, Pandolfi PP. Cancer metabolism: fatty acid oxidation in the limelight. Nat Rev Cancer ; 13 : — Jeon SM, Chandel NS, Hay N.

AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Zaugg K, Yao Y, Reilly PT, Kannan K, Kiarash R, Mason J et al. Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress. Genes Dev ; 25 : — Caro P, Kishan AU, Norberg E, Stanley IA, Chapuy B, Ficarro SB et al.

Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma. Cancer Cell ; 22 : — Pike LS, Smift AL, Croteau NJ, Ferrick DA, Wu M.

Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells.

Biochim Biophys Acta ; : — Samudio I, Harmancey R, Fiegl M, Kantarjian H, Konopleva M, Korchin B et al. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J Clin Invest ; : — Riganti C, Gazzano E, Polimeni M, Aldieri E, Ghigo D.

The pentose phosphate pathway: an antioxidant defense and a crossroad in tumor cell fate. Free Radic Biol Med ; 53 : — Patra KC, Hay N. The pentose phosphate pathway and cancer.

Trends Biochem Sci ; 39 : — Du W, Jiang P, Mancuso A, Stonestrom A, Brewer MD, Minn AJ et al. TAp73 enhances the pentose phosphate pathway and supports cell proliferation. Nat Cell Biol ; 15 : — D'Alessandro A, Amelio I, Berkers CR, Antonov A, Vousden KH, Melino G et al.

Metabolic effect of TAp63alpha: enhanced glycolysis and pentose phosphate pathway, resulting in increased antioxidant defense. Oncotarget ; 5 : — PubMed PubMed Central Google Scholar.

Lucarelli G, Galleggiante V, Rutigliano M, Sanguedolce F, Cagiano S, Bufo P et al. Metabolomic profile of glycolysis and the pentose phosphate pathway identifies the central role of glucosephosphate dehydrogenase in clear cell-renal cell carcinoma.

Oncotarget ; 6 : — Polimeni M, Voena C, Kopecka J, Riganti C, Pescarmona G, Bosia A et al. Modulation of doxorubicin resistance by the glucosephosphate dehydrogenase activity. Biochem J ; : — Yin L, Kufe T, Avigan D, Kufe D.

Targeting MUC1-C is synergistic with bortezomib in downregulating TIGAR and inducing ROS-mediated myeloma cell death. Blood ; : — Sharma PK, Bhardwaj R, Dwarakanath BS, Varshney R. Metabolic oxidative stress induced by a combination of 2-DG and 6-AN enhances radiation damage selectively in malignant cells via non-coordinated expression of antioxidant enzymes.

Ruiz-Perez MV, Sanchez-Jimenez F, Alonso FJ, Segura JA, Marquez J, Medina MA. Glutamine, glucose and other fuels for cancer.

Curr Pharm Des ; 20 : — Daye D, Wellen KE. Metabolic reprogramming in cancer: unraveling the role of glutamine in tumorigenesis. Semin Cell Dev Biol ; 23 : — Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK et al. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction.

Cetinbas N, Daugaard M, Mullen AR, Hajee S, Rotblat B, Lopez A et al. Loss of the tumor suppressor Hace1 leads to ROS-dependent glutamine addiction.

Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M et al. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Le A, Lane AN, Hamaker M, Bose S, Gouw A, Barbi J et al. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells.

Cell Metab ; 15 : — Sato H, Tamba M, Ishii T, Bannai S. Mates JM, Segura JA, Martin-Rufian M, Campos-Sandoval JA, Alonso FJ, Marquez J. Glutaminase isoenzymes as key regulators in metabolic and oxidative stress against cancer.

Curr Mol Med ; 13 : — Lyssiotis CA, Son J, Cantley LC, Kimmelman AC. Pancreatic cancers rely on a novel glutamine metabolism pathway to maintain redox balance. Cell Cycle ; 12 : — Hensley CT, Wasti AT, DeBerardinis RJ. Glutamine and cancer: cell biology, physiology, and clinical opportunities.

Xiang Y, Stine ZE, Xia J, Lu Y, O'Connor RS, Altman BJ et al. Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis.

Seltzer MJ, Bennett BD, Joshi AD, Gao P, Thomas AG, Ferraris DV et al. Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1.

Cancer Res ; 70 : — Emadi A, Jun SA, Tsukamoto T, Fathi AT, Minden MD, Dang CV. Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations.

Exp Hematol ; 42 : — Goto M, Miwa H, Shikami M, Tsunekawa-Imai N, Suganuma K, Mizuno S et al. Importance of glutamine metabolism in leukemia cells by energy production through TCA cycle and by redox homeostasis.

Cancer Invest ; 32 : — Izaki S, Goto H, Yokota S. Increased chemosensitivity and elevated reactive oxygen species are mediated by glutathione reduction in glutamine deprived neuroblastoma cells. J Cancer Res Clin Oncol ; : — Locasale JW. Serine, glycine and one-carbon units: cancer metabolism in full circle.

DeBerardinis RJ. Serine metabolism: some tumors take the road less traveled. Cell Metab ; 14 : — Amelio I, Cutruzzola F, Antonov A, Agostini M, Melino G. Serine and glycine metabolism in cancer.

Chouchani ET, Pell VR, Gaude E, Aksentijevic D, Sundier SY, Robb EL et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Martinez-Reyes I, Chandel NS. Mitochondrial one-carbon metabolism maintains redox balance during hypoxia. Cancer Discov ; 4 : — Lewis CA, Parker SJ, Fiske BP, McCloskey D, Gui DY, Green CR et al.

Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells. Molecular cell ; 55 : — Ye J, Fan J, Venneti S, Wan YW, Pawel BR, Zhang J et al. Serine catabolism regulates mitochondrial redox control during hypoxia. DeNicola GM, Chen PH, Mullarky E, Sudderth JA, Hu Z, Wu D et al.

NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nat Genet ; 47 : — Daidone F, Florio R, Rinaldo S, Contestabile R, di Salvo ML, Cutruzzola F et al.

In silico and in vitro validation of serine hydroxymethyltransferase as a chemotherapeutic target of the antifolate drug pemetrexed. Eur J Med Chem ; 46 : — Handy DE, Loscalzo J.

Redox regulation of mitochondrial function. Antioxid Redox Signal ; 16 : — Finkel T. Signal transduction by mitochondrial oxidants. Han D, Antunes F, Canali R, Rettori D, Cadenas E. Voltage-dependent anion channels control the release of the superoxide anion from mitochondria to cytosol.

Lustgarten MS, Bhattacharya A, Muller FL, Jang YC, Shimizu T, Shirasawa T et al. Complex I generated, mitochondrial matrix-directed superoxide is released from the mitochondria through voltage dependent anion channels.

Murphy MP. Mitochondrial thiols in antioxidant protection and redox signaling: distinct roles for glutathionylation and other thiol modifications. Weinberg F, Hamanaka R, Wheaton WW, Weinberg S, Joseph J, Lopez M et al.

Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Smith RA, Murphy MP. Animal and human studies with the mitochondria-targeted antioxidant MitoQ. Ann NY Acad Sci ; : 96— Rao VA, Klein SR, Bonar SJ, Zielonka J, Mizuno N, Dickey JS et al.

The antioxidant transcription factor Nrf2 negatively regulates autophagy and growth arrest induced by the anticancer redox agent mitoquinone. Nilsson R, Jain M, Madhusudhan N, Sheppard NG, Strittmatter L, Kampf C et al.

Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer.

Lehtinen L, Ketola K, Makela R, Mpindi JP, Viitala M, Kallioniemi O et al. High-throughput RNAi screening for novel modulators of vimentin expression identifies MTHFD2 as a regulator of breast cancer cell migration and invasion.

Oncotarget ; 4 : 48— Article PubMed Google Scholar. Sharma LK, Fang H, Liu J, Vartak R, Deng J, Bai Y. Mitochondrial respiratory complex I dysfunction promotes tumorigenesis through ROS alteration and AKT activation.

Hum Mol Genet ; 20 : — Sullivan LB, Chandel NS. Mitochondrial reactive oxygen species and cancer. Cancer Metab ; 2 : Ray PD, Huang BW, Tsuji Y.

Reactive oxygen species ROS homeostasis and redox regulation in cellular signaling. Cell Signal ; 24 : — Ward PS, Thompson CB. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell ; 21 : — DeBerardinis RJ, Cheng T.

Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene ; 29 : — Mullen AR, Wheaton WW, Jin ES, Chen PH, Sullivan LB, Cheng T et al. Reductive carboxylation supports growth in tumour cells with defective mitochondria.

Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia.

Woo DK, Green PD, Santos JH, D'Souza AD, Walther Z, Martin WD et al. Am J Pathol ; : 24— Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H et al. ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis.

Porporato PE, Payen VL, Perez-Escuredo J, De Saedeleer CJ, Danhier P, Copetti T et al. A mitochondrial switch promotes tumor metastasis.

Cell Rep ; 8 : — Fan J, Kamphorst JJ, Mathew R, Chung MK, White E, Shlomi T et al. Glutamine-driven oxidative phosphorylation is a major ATP source in transformed mammalian cells in both normoxia and hypoxia. Mol Syst Biol ; 9 : Haq R, Shoag J, Andreu-Perez P, Yokoyama S, Edelman H, Rowe GC et al.

Oncogenic BRAF regulates oxidative metabolism via PGC1alpha and MITF. Cancer Cell ; 23 : — Vazquez F, Lim JH, Chim H, Bhalla K, Girnun G, Pierce K et al. The role of plant mitochondria in cell death and stress resistance is receiving progressively more attention. Although our knowledge is increasing in this domain, most information comes from studies with respiratory inhibitors, and the interpretation of such studies must be done with caution because of the lack of specificity and the inherent problem of distinguishing the engagement and capacity of respiratory pathways.

Very recently, Lee et al. By contrast, no such damage was detected in the N. sylvestris complex I mutant analyzed in this study our unpublished results. Furthermore, the data presented here show unambiguously that the lack of complex I activity in N.

sylvestris was associated with enhanced tolerance to oxidative stress induced by ozone and TMV. Comparison of these two studies is rendered difficult by the absence of complete information on the structural and functional effects of the lesion in the Arabidopsis complex.

It is possible that, in contrast to the deletion of the mitochondrial nad7 gene in CMSII, disruption of the nuclear gene that encodes the kD subunit has no effect on complex I assembly and activity, as was found in several complex I mutants of Neurospora Videira, ; therefore, it may not be associated with the activation of AOX and antioxidant components, as observed here.

This would explain the differences between Arabidopsis and N. sylvestris mutants. It is not possible to speculate further, in the absence of information on the actual perturbation of respiration in the Arabidopsis mutant.

For CMSII, we reported previously that the mutant shows modified metabolism e. Data presented here show that this readjustment of respiratory metabolism is associated with a temporal and spatial redistribution of the antioxidant system coupled with increased antioxidant capacity that may account for the enhanced resistance to oxidative stress.

The present data allow us to draw the following conclusions. Much less information is available for plants than for animals about the role of mitochondria in the maintenance of the whole cell redox state. In plants, many studies have focused on the role of the AOX, which has been proposed to be involved in the control of H 2 O 2 levels in plant cells Wagner and Moore, Accordingly, H 2 O 2 levels were decreased in tobacco cells overexpressing the AOX gene Maxwell et al.

A previous study has indicated that the loss of complex I function in CMSII is associated with the induction of AOX Gutierres et al. The present study demonstrates that the induction of AOX is associated with lower global H 2 O 2 levels, whereas there are no marked changes in glutathione and ascorbate pools.

Most importantly, these key antioxidants remain in the highly reduced state compatible with continued cell function. Because enhanced nonphosphorylating electron transport via AOX when complex I is nonfunctional is expected to decrease mitochondrial ATP yields further, our data suggest that maintenance of the cellular redox state takes precedence over ATP production.

Together, these results strongly suggest that despite complex I dysfunction, there is no constitutive oxidative stress in CMSII photosynthetic tissues. Therefore, these results are in contrast to those reported for the Arabidopsis complex I mutant, in which increased DAB staining was detected Lee et al.

As in animal mitochondria, two types of mechanisms limit AOS accumulation in plants. The first involves the avoidance of AOS production and is facilitated in plants by the presence of the nonphosphorylating respiratory enzymes NAD P H dehydrogenases and AOX Wagner and Moore, ; Møller, Induction of AOX under stress conditions has been reported in a number of plant systems, particularly in relation to H 2 O 2 accumulation.

For example, AOX has been shown to be induced by H 2 O 2 Wagner, , and inhibition of the alternative oxidase stimulates H 2 O 2 production Popov et al.

Moreover, H 2 O 2 content was decreased in N. tabacum cells overexpressing the AOX gene Maxwell et al. The second defense strategy consists of the recruitment of AOS-scavenging enzymes. Components relating to both strategies are activated in CMSII mitochondria, because both AOX and MnSOD transcripts were increased in association with decreased H 2 O 2.

In agreement with our results, Pitkanen and Robinson have shown the induction of MnSOD in patients suffering from complex I dysfunction. Thus, our observations strongly suggest that in CMSII the expression of both MnSOD and AOX is responsive to local mitochondrial production of AOS and that signals emitted as a result cause the acclimation that increases the capacity for scavenging to prevent AOS accumulation.

In any aerobic system, redox homeostasis depends on the balance between production and removal. The striking upregulation of AOX represents a local avoidance strategy, whereas that of MnSOD is part of a local defense scavenging tactic.

Even more importantly, our data show that the signaled redox acclimation extends far beyond the mitochondria. The induction of local mitochondrial components in CMSII was accompanied by the remote upregulation of AOS-processing systems in other cell compartments.

Steady state transcript levels for CAT2 and CAT3 targeted to microbodies such as peroxisomes and glyoxysomes , FeSOD targeted to chloroplasts , and cAPX targeted to the cytosol all were more abundant in CMSII than in wild-type leaves.

This finding suggests that mitochondrial signals control either rates of transcription or rates of turnover of mRNA that encodes these enzymes or both. We recently discussed the modified redox dialog between compartments with regard to primary metabolism and the increased activation state of NADP—malate dehydrogenase activity in CMSII Dutilleul et al.

Indeed, because AOS formation is virtually impossible to measure, induction of the antioxidant system frequently is taken as a marker for enhanced AOS production.

If this is so, our data suggest that reactive oxygen species sensors in the mitochondria markedly influence the expression of antioxidative genes throughout the cell. Not only is AOX induced in CMSII, but its diurnal regulation is inverted. In the wild type, AOX transcript abundance was very low during the night, and the AOX protein was hardly detectable.

The daily rhythms of some other antioxidant transcripts also were altered, although to a lesser extent than that of AOX. Numerous plant antioxidant genes showed diurnal rhythms interacting with the circadian clock. Similar to N. sylvestris cAPX Figure 5 , the Arabidopsis cAPX transcripts peak during the light period Kubo et al.

In wild-type N. This diurnal pattern became even more pronounced in CMSII, in which the relative contributions of CAT2 and CAT3 were increased, especially at the end of the light period.

By contrast, the diurnal rhythms of chlFeSOD and cAPX were attenuated in the mutant. These data suggest, first, that engagement of redox signaling overrides the control of diurnal rhythms by the circadian clock, and second, that mitochondria provide trig-gers for the network involved in diurnal rhythms in gene expression.

One example is the daily rhythm of AOX transcripts, which is less apparent at the protein level. The increase in GR activity in CMSII, which is unrelated to increases in transcripts, also indicates that the readjustment of the antioxidative system in CMSII is a multilevel phenomenon that involves transcriptional and post-transcriptional events.

This effect could be related to the slower growth and delayed senescence in the mutant. At the flowering stage, CMSII mature leaves remain healthy for several weeks, whereas they rapidly become senescent in the wild type.

Again, these features are indicative of the absence of oxidative stress in the mutant. The relationships between aging, AOS generation, and induction of the antioxidative system have been known for many years Thompson et al. Our data indicate that mitochondria-linked control of redox state is a significant player in the regulation of leaf senescence.

A number of specific antioxidant genes are induced to cope with enhanced AOS production during oxidative stress Bartosz, For example, Arabidopsis cAPX transcripts are increased after exposure to high light Karpinski et al.

By contrast, chlAPX expression is not changed by these stresses. Enhanced tolerance to ozone has been shown in tobacco plants that overexpress MnSOD Van Camp et al. In good agreement, our data show that CMSII, with increased expression of AOX , MnSOD , and cAPX , has enhanced tolerance to ozone.

The response of cAPX and AOX transcripts shows that ozone is not excluded from the leaves of either genotype and suggests that resistance to ozone is linked mainly to increased antioxidant capacity. In addition to increased resistance to ozone, lack of complex I activity is associated with differences in hypersensitive response—induced responses to both viral and bacterial elicitors.

We recently reported differences in antioxidant and defense gene expression between wild-type and CMSII leaves inoculated with a bacterial elicitor Boccara et al. Here, we show that the number and size of N gene—induced lesions were attenuated markedly in N.

tabacum N hybrids carrying the CMSII cytoplasm. Moreover, amounts of TMV capsidial protein were reduced in the lesions. This finding suggests that CMSII N plants are more resistant to TMV than wild-type plants, because multiplication of the virus is hindered Figure 8E by the high level of leaf antioxidant enzymes.

tabacum NN plants, in which antioxidant enzyme levels were increased after exposure to oxidative stress, were shown to be more resistant to TMV in an incompatible interaction Mittler et al. The possible involvement of AOX in plant resistance and programmed cell death also has given rise to much interest and debate.

Increased AOX protein levels have been found in both bacterial Simons et al. However, although AOX protein was more abundant in N.

tabacum NN inoculated with TMV, in vivo engagement of the enzyme remained unaffected Lennon et al. Recently, the proportion of cell death was found to be related to the level of AOX expression in tobacco cell cultures Robson and Vanlerberghe, ; Vanlerberghe et al.

tabacum NN plants overexpressing AOX Ordog et al. By contrast, TMV-susceptible N. tabacum plants overexpressing AOX did not show improved resistance to the virus Ordog et al. Accordingly, we did not detect differences in viral replication between the wild type and CMSII in the compatible TMV interaction our unpublished results.

Thus, it seems that although they are possibly involved in the establishment of the hypersensitive response, AOX and other antioxidants do not necessarily confer better resistance to a compatible pathogen. It is possible that the upregulation of AOX that we observed in CMSII may be accompanied by decreased cytochrome pathway components, which may influence cell death susceptibility, because, as in animals, cytochrome c release is involved in programmed cell death in plants Balk et al.

Although considered a major source of AOS in nonphotosynthetic tissues and in photosynthetic tissues in the dark, mitochondria are expected to contribute only a small fraction of total leaf AOS production in the light. Despite this fact, CMSII leaves show induction of the antioxidative system in both the light and the dark.

Associated with this induction is enhanced stress resistance. Recent data show that the response to oxidative stress involves numerous genes, and not only those involved directly in the control of AOS Vranova et al. Therefore, we expect that enhanced stress resistance may not result solely from the upregulation of antioxidative components.

However, this upregulation is a clear marker for the long-term acclimatory activation of stress resistance in response to the loss of a major mitochondrial NADH dehydrogenase. These mitochondrion-specific signals are relayed to the nucleus by transducers dotted line , leading to the effects observed in CMSII.

These effects are as follows: increased abundance of transcripts of antioxidative enzymes that process locally generated AOS species MnSOD or decrease their rate of production AOX in mitochondria [1]; and whole cell induction of transcripts that encode antioxidative enzymes located in compartments CAT1, CAT3, cAPX, and FeSOD external to the mitochondria [2].

Together, these acclimatory responses trigger decreased whole cell reactive oxygen species ROS accumulation and enhance stress resistance [3].

Nicotiana sylvestris is the diploid maternal ancestor of the tetraploid cultivated tobacco, Nicotiana tabacum. The N. sylvestris wild parental type is a fertile botanical line of the Institut des Tabacs Bergerac, France. The CMSII mutant was obtained by in vitro wild-type protoplast culture Li et al.

Irrigation was supplemented with macronutrients. Samples taken were from the second well-developed leaves. For RNA isolation, leaf tissue pieces 0.

Total RNAs were extracted by the Trizol-chloroform procedure Gibco BRL. Ten micrograms of total RNA was fractionated on a 1. Homologous probes were Nicotiana plumbaginifolia CAT1 , CAT2 , and CAT3 Willekens et al. tabacum plastidial GR Creissen and Mullineaux, , N.

tabacum cAPX Orvar and Ellis, , N. plumbaginifolia MnSOD1 Bowler et al. plumbaginifolia FeSOD Van Camp et al. sylvestris AOX probe Sabar et al. tabacum chlAPX sequence Yoshimura et al. All procedures for blot analysis were performed as described previously Sabar et al. Quantification of the relative abundance of transcripts was determined using a scanning densitometer MasterScan; Scanalytics, Billerica, MA.

Leaf material 0. To distinguish between chloroplastic and nonchloroplastic extractable APX activities, samples were extracted in the presence or absence of 5 mM ascorbate in the medium. The extract was centrifuged for 5 min at 15, g , and protein was determined according to Bradford The following antisera were used: mice monoclonal antiserum against Sauromatum guttatum AOX Elthon et al.

Horseradish peroxidase—conjugated goat anti-mouse or anti-rabbit IgG was used as a secondary antibody at a dilution of , and immune complexes were visualized by the color reaction of peroxidase as described by Gutierres et al.

Global leaf H 2 O 2 was determined according to the method of Veljovic-Jovanovic et al. In situ O 2. Leaf discs were punched out with a cork borer 2 cm in diameter from the central area of the second fully developed leaf and vacuum-infiltrated three cycles of 5 min in 0.

As a control, DAB solution was supplemented with 10 mM ascorbic acid before infiltration. H 2 O 2 was visualized as brown color at the site of DAB polymerization. Leaf discs 2. After thawing, samples were centrifuged for 15 min at 15, g and 4°C.

The pH of the clarified supernatant was adjusted to 5. Ascorbate and glutathione were measured in the same supernatant. Total and reduced ascorbate contents were measured as the ascorbate oxidase—dependent decrease in A before reduced ascorbate and after total ascorbate treatment of the sample for 15 min with 0.

The 1-mL reaction mixture contained 0. Total and oxidized glutathione contents were measured using the enzymatic recycling assay, which involves the NADPH-driven glutathione-dependent reduction of 5,5-dithiobis 2-nitrobenzoic acid at nm Noctor and Foyer, b. Wild-type and CMSII N. tabacum hybrid plants, at the same developmental stage first flower bud , were inoculated with the common U1 strain of TMV.

Lesions were evaluated 7 days after inoculation. The significance of differences was determined using Student's t test. Upon request, all novel materials described in this article will be made available in a timely manner for noncommercial research purposes.

We gratefully acknowledge the following for the gifts of probes: D. Inzé SOD and CAT cDNA probes , B. Ellis cAPX probe , G. Creissen chlGR probe , T. Elthon AOX antibody , J.

Feierabend CAT antibody , and A. Kubo cAPX antibody. We thank S. Kauffmann for providing the TMV U1 strain and Roland Boyer for photographic work. Many thanks to M. Boccara for helpful discussion and comments.

This work was supported by the Centre National de la Recherche Scientifique France , the Biotechnology and Biological Science Research Council United Kingdom , the British Council Alliance program funding , the European Science Foundation fellowship award to C.

Alscher, R. Reactive oxygen species and antioxidants: Relationships in green cells. Amako, K. Separate assays specific for ascorbate peroxidase and guaiacol peroxidase and for chloroplastic and cytosolic isozymes of ascorbate peroxidase in plants.

Plant Cell Physiol. Asada, K. Ascorbate peroxidase: A hydrogen peroxide-scavenging enzyme in plants. Balk, J. Translocation of cytochrome c from the mitochondria to the cytosol occurs during heat-induced programmed cell death in cucumber plants.

FEBS Lett. Bartosz, G. Oxidative stress in plants. Acta Physiol. Boccara, M. IR thermography revealed a role for mitochondria in presymptomatic cooling during harpin-induced hypersensitive response. Plant J. Bowler, C. The induction of manganese superoxide dismutase in response to stress in Nicotiana plumbaginifolia.

EMBO J. Superoxide dismutase and stress tolerance. Plant Physiol. Plant Mol. Bradford, M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Braidot, E. Hydrogen peroxide generation by higher plant mitochondria oxidizing complex I or complex II substrates.

Chivasa, S. Cyanide restores N gene—mediated resistance to tobacco mosaic virus in transgenic tobacco expressing salicylic acid hydroxylase. Plant Cell 10 , — Cotovio, J. Generation of oxidative stress in human cutaneous models following in vitro ozone exposure. in Vitro 15 , — Creissen, G.

Cloning and characterisation of glutathione reductase cDNAs and identification of two genes encoding the tobacco enzyme. Planta , — Dawson, W.

Tobacco mosaic virus virulence and avirulence. B , — Day, D. Regulation of alternative oxidase activity in higher plants. De Paepe, R. Several nuclear genes control both sterility and mitochondrial protein synthesis in Nicotiana sylvestris protoclones. Donahue, J.

Thank you for visiting nature. You are Plant-based ingredients a homeostzsis version with limited support for Antioxdant. To obtain Antiooxidant best experience, we recommend Antioxidant homeostasis use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Tumor cells harbor genetic alterations that promote a continuous and elevated production of reactive oxygen species. DOI: Antioxidant homeostasis Reactive oxygen species are Antioxidant homeostasis result of normal oxygen metabolism, which even possess the Antioxirant to damage the cells; and thus, Antioxidant homeostasis Antilxidant necessary to homeostasiz them. Redox homeostasis is a natural mechanism that detoxifies these ROS and involves many cellular processes in the detoxification. However, the production of ROS increases dramatically during environmental stress, which can result in the disruption of redox homeostasis. This disruption can lead to several complications that include the generation of tumour cells, ageing, diabetes and neurodegeneration.

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