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
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
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
Fatokun AA, Dawson VL, Dawson TM (2014) Parthanatos: mitochondrial-linked mechanisms and therapeutic opportunities. Br J Pharmacol 171:2000–2016
Andreux PA, Houtkooper RH, Auwerx J (2013) Pharmacological approaches to restore mitochondrial function. Nat Rev Drug Discov 12:465–483
DuBoff B, Feany M, Gotz J (2013) Why size matters - balancing mitochondrial dynamics in Alzheimer's disease. Trends Neurosci 36:325–335
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
Nunnari J, Suomalainen A (2012) Mitochondria: in sickness and in health. Cell 148:1145–1159
Adam-Vizi V, Chinopoulos C (2006) Bioenergetics and the formation of mitochondrial reactive oxygen species. Trends Pharmacol Sci 27:639–645
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
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
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
Cantó C, Sauve A, Bai P (2013) Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes. Mol Asp Med 34:1168–1201
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
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
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
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
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
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
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
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
Brummelkamp TR, Bernards R, Agami R (2002) A system for stable expression of short interfering RNAs in mammalian cells. Science 296:550–553
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
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
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
Antolin AA, Mestres J (2014) Linking off-target kinase pharmacology to the differential cellular effects observed among PARP inhibitors. Oncotarget 10:10
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
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
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
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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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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