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Methods to Assess the Role of Poly(ADP-Ribose) Polymerases in Regulating Mitochondrial Oxidation

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Poly(ADP-Ribose) Polymerase

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1608))

Abstract

The impact of poly(ADP-ribose) polymerase (PARP) enzymes on cellular NAD+ has been established for almost 30 years now and its sequel, the metabolic collapse of cells upon PARP overactivation is a nearly 20-year-old observation. However, in the last decade there was an enormous blooming in the understanding of the interplay between PARPs and mitochondria. Mitochondrial activity can be assessed by a comprehensive set of methods that we aim to introduce here.

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References

  1. Virag L, Salzman AL, Szabo C (1998) Poly(ADP-ribose) synthetase activation mediates mitochondrial injury during oxidant-induced cell death. J Immunol 161:3753–3759

    CAS  PubMed  Google Scholar 

  2. Yu SW, Wang H, Poitras MF, Coombs C, Bowers WJ, Federoff HJ, Poirier GG, Dawson TM, Dawson VL (2002) Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science 297:259–263

    Article  CAS  PubMed  Google Scholar 

  3. Fatokun AA, Dawson VL, Dawson TM (2014) Parthanatos: mitochondrial-linked mechanisms and therapeutic opportunities. Br J Pharmacol 171:2000–2016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Andreux PA, Houtkooper RH, Auwerx J (2013) Pharmacological approaches to restore mitochondrial function. Nat Rev Drug Discov 12:465–483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. DuBoff B, Feany M, Gotz J (2013) Why size matters - balancing mitochondrial dynamics in Alzheimer's disease. Trends Neurosci 36:325–335

    Article  CAS  PubMed  Google Scholar 

  6. Wen Y, Li W, Poteet EC, Xie L, Tan C, Yan LJ, Ju X, Liu R, Qian H, Marvin MA et al (2011) Alternative mitochondrial electron transfer as a novel strategy for neuroprotection. J Biol Chem 286:16504–16515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Nunnari J, Suomalainen A (2012) Mitochondria: in sickness and in health. Cell 148:1145–1159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Adam-Vizi V, Chinopoulos C (2006) Bioenergetics and the formation of mitochondrial reactive oxygen species. Trends Pharmacol Sci 27:639–645

    Article  CAS  PubMed  Google Scholar 

  9. Virag L, Szabo C (2000) BCL-2 protects peroxynitrite-treated thymocytes from poly(ADP-ribose) synthase (PARS)-independent apoptotic but not from PARS-mediated necrotic cell death. Free Radic Biol Med 29:704–713

    Article  CAS  PubMed  Google Scholar 

  10. Bai P, Nagy L, Fodor T, Liaudet L, Pacher P (2015) Poly(ADP-ribose) polymerases as modulators of mitochondrial activity. Trends Endocrinol Metab 26:75–83

    Article  CAS  PubMed  Google Scholar 

  11. Formentini L, Macchiarulo A, Cipriani G, Camaioni E, Rapizzi E, Pellicciari R, Moroni F, Chiarugi A (2009) Poly(ADP-ribose) catabolism triggers AMP-dependent mitochondrial energy failure. J Biol Chem 284:17668–17676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cantó C, Sauve A, Bai P (2013) Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes. Mol Asp Med 34:1168–1201

    Article  Google Scholar 

  13. Houtkooper RH, Canto C, Wanders RJ, Auwerx J (2010) The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. Endocr Rev 31:194–223

    Article  CAS  PubMed  Google Scholar 

  14. Brunyanszki A, Szczesny B, Virag L, Szabo C (2016) Mitochondrial poly(ADP-ribose) polymerase: the wizard of Oz at work. Free Radic Biol Med 8:00075–00077

    Google Scholar 

  15. Pirinen E, Cantó E, Jo SK, Morato L, Zhang H, Menzies KJ, Williams EG, Mouchiroud L, Moullan N, Hagberg C et al (2014) Pharmacological inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle. Cell Metab 19:1034–1041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mouchiroud L, Houtkooper RH, Moullan N, Katsyuba E, Ryu D, Canto C, Mottis A, Jo YS, Viswanathan M, Schoonjans K et al (2013) The NAD(+)/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell 154:430–441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Houtkooper RH, Mouchiroud L, Ryu D, Moullan N, Katsyuba E, Knott G, Williams RW, Auwerx J (2013) Mitonuclear protein imbalance as a conserved longevity mechanism. Nature 497:451–457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bai P, Canto C, Brunyanszki A, Huber A, Szanto M, Cen Y, Yamamoto H, Houten SM, Kiss B, Oudart H et al (2011) PARP-2 regulates SIRT1 expression and whole-body energy expenditure. Cell Metab 13:450–460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Szántó M, Rutkai I, Hegedus C, Czikora A, Rózsahegyi M, Kiss B, Virág L, Gergely P, Tóth A, Bai P (2011) Poly(ADP-ribose) polymerase-2 depletion reduces doxorubicin-induced damage through SIRT1 induction. Cardiovasc Res 92:430–438

    Article  PubMed  Google Scholar 

  20. Szántó M, Brunyánszki A, Márton J, Vámosi G, Nagy L, Fodor T, Kiss B, Virág L, Gergely P, Bai P (2014) Deletion of PARP-2 induces hepatic cholesterol accumulation and decrease in HDL levels. BBA-Mol Basis Dis 1842:594–602

    Article  Google Scholar 

  21. Brummelkamp TR, Bernards R, Agami R (2002) A system for stable expression of short interfering RNAs in mammalian cells. Science 296:550–553

    Article  CAS  PubMed  Google Scholar 

  22. Bai P, Houten SM, Huber A, Schreiber V, Watanabe M, Kiss B, de Murcia G, Auwerx J, Menissier-de Murcia J (2007) Poly(ADP-ribose) polymerase-2 controls adipocyte differentiation and adipose tissue function through the regulation of the activity of the retinoid X receptor/peroxisome proliferator-activated receptor-gamma heterodimer. J Biol Chem 282:37738–37746

    Article  CAS  PubMed  Google Scholar 

  23. Fodor T, Szanto M, Abdul-Rahman O, Nagy L, Der A, Kiss B, Bai P (2016) Combined treatment of MCF-7 cells with AICAR and methotrexate, arrests cell cycle and reverses Warburg metabolism through AMP-Activated Protein Kinase (AMPK) and FOXO1. PLoS One 11:e0150232. doi: 0150210.0151371/journal.pone.0150232. eCollection 0152016

    Article  PubMed  PubMed Central  Google Scholar 

  24. Antolin AA, Jalencas X, Yelamos J, Mestres J (2012) Identification of Pim kinases as novel targets for PJ34 with confounding effects in PARP biology. ACS Chem Biol. doi:10.1021/cb300317y

    PubMed  Google Scholar 

  25. Antolin AA, Mestres J (2014) Linking off-target kinase pharmacology to the differential cellular effects observed among PARP inhibitors. Oncotarget 10:10

    Google Scholar 

  26. Bai P, Canto C, Oudart H, Brunyanszki A, Cen Y, Thomas C, Yamamoto H, Huber A, Kiss B, Houtkooper RH et al (2011) PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation. Cell Metab 13:461–468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Abdul-Rahman O, Kristóf E, Doan-Xuan QM, Vida A, Horváth A, Simon J, Maros T, Szentkirályi I, Palotás L, Debreceni T et al (2016) AMP-activated kinase (AMPK) activation by AICAR in human white adipocytes derived from pericardial white adipose tissue stem cells induces a partial beige-like phenotype. PLoS One 11(6):e0157644. doi:10.1371/journal.pone.0157644. eCollection 2016

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P et al (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127:1109–1122

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

Our work was supported by grants from NKFIH (K108308, K105872, K120416, C129074, C209584), TÁMOP-4.2.2. A-11/1/KONV-2012-0025, the Momentum fellowship of the Hungarian Academy of Sciences, and the University of Debrecen.

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Authors and Affiliations

  1. Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Egyetem tér 1, Debrecen, H-4032, Hungary

    Edit Mikó, Tünde Kovács, Tamás Fodor & Péter Bai Ph.D., D.Sc.

  2. Lendület Laboratory of Cellular Metabolism, MTA-DE, Debrecen, H-4032, Hungary

    Edit Mikó & Péter Bai Ph.D., D.Sc.

  3. Research Center for Molecular Medicine, University of Debrecen, Debrecen, H-4032, Hungary

    Péter Bai Ph.D., D.Sc.

Authors
  1. Edit Mikó
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  2. Tünde Kovács
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  3. Tamás Fodor
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  4. Péter Bai Ph.D., D.Sc.
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Corresponding author

Correspondence to Péter Bai Ph.D., D.Sc. .

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Editors and Affiliations

  1. Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

    Alexei V. Tulin

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Mikó, E., Kovács, T., Fodor, T., Bai, P. (2017). Methods to Assess the Role of Poly(ADP-Ribose) Polymerases in Regulating Mitochondrial Oxidation. In: Tulin, A. (eds) Poly(ADP-Ribose) Polymerase. Methods in Molecular Biology, vol 1608. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6993-7_13

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  • DOI: https://doi.org/10.1007/978-1-4939-6993-7_13

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6992-0

  • Online ISBN: 978-1-4939-6993-7

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