PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation

Péter Bai; Carles Cantó; Hugues Oudart; Attila Brunyánszki; Yana Cen; Charles Thomas; Hiroyasu Yamamoto; Aline Huber; Borbála Kiss; Riekelt H. Houtkooper; Kristina Schoonjans; Valérie Schreiber; Anthony A. Sauve; Josiane Menissier-de Murcia; Johan Auwerx

doi:https://doi.org/10.1016/j.cmet.2011.03.004

PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation

Péter Bai, Carles Cantó, Hugues Oudart, Attila Brunyánszki, Yana Cen, Charles Thomas, Hiroyasu Yamamoto, Aline Huber, Borbála Kiss, Riekelt H. Houtkooper, Kristina Schoonjans, Valérie Schreiber, Anthony A. Sauve, Josiane Menissier-de Murcia, Johan Auwerx

Research output: Contribution to journal › Article › Academic › peer-review

647 Citations (Scopus)

Abstract

SIRT1 regulates energy homeostasis by controlling the acetylation status and activity of a number of enzymes and transcriptional regulators. The fact that NAD(+) levels control SIRT1 activity confers a hypothetical basis for the design of new strategies to activate SIRT1 by increasing NAD(+) availability. Here we show that the deletion of the poly(ADP-ribose) polymerase-1 (PARP-1) gene, encoding a major NAD(+)-consuming enzyme, increases NAD(+) content and SIRT1 activity in brown adipose tissue and muscle. PARP-1(-/-) mice phenocopied many aspects of SIRT1 activation, such as a higher mitochondrial content, increased energy expenditure, and protection against metabolic disease. Also, the pharmacologic inhibition of PARP in vitro and in vivo increased NAD(+) content and SIRT1 activity and enhanced oxidative metabolism. These data show how PARP-1 inhibition has strong metabolic implications through the modulation of SIRT1 activity, a property that could be useful in the management not only of metabolic diseases, but also of cancer

Original language	English
Pages (from-to)	461-468
Journal	Cell metabolism
Volume	13
Issue number	4
DOIs	https://doi.org/10.1016/j.cmet.2011.03.004
Publication status	Published - 2011

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https://doi.org/10.1016/j.cmet.2011.03.004

Cite this

Bai, P., Cantó, C., Oudart, H., Brunyánszki, A., Cen, Y., Thomas, C., Yamamoto, H., Huber, A., Kiss, B., Houtkooper, R. H., Schoonjans, K., Schreiber, V., Sauve, A. A., Menissier-de Murcia, J., & Auwerx, J. (2011). PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation. Cell metabolism, 13(4), 461-468. https://doi.org/10.1016/j.cmet.2011.03.004

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title = "PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation",

abstract = "SIRT1 regulates energy homeostasis by controlling the acetylation status and activity of a number of enzymes and transcriptional regulators. The fact that NAD(+) levels control SIRT1 activity confers a hypothetical basis for the design of new strategies to activate SIRT1 by increasing NAD(+) availability. Here we show that the deletion of the poly(ADP-ribose) polymerase-1 (PARP-1) gene, encoding a major NAD(+)-consuming enzyme, increases NAD(+) content and SIRT1 activity in brown adipose tissue and muscle. PARP-1(-/-) mice phenocopied many aspects of SIRT1 activation, such as a higher mitochondrial content, increased energy expenditure, and protection against metabolic disease. Also, the pharmacologic inhibition of PARP in vitro and in vivo increased NAD(+) content and SIRT1 activity and enhanced oxidative metabolism. These data show how PARP-1 inhibition has strong metabolic implications through the modulation of SIRT1 activity, a property that could be useful in the management not only of metabolic diseases, but also of cancer",

author = "P{\'e}ter Bai and Carles Cant{\'o} and Hugues Oudart and Attila Bruny{\'a}nszki and Yana Cen and Charles Thomas and Hiroyasu Yamamoto and Aline Huber and Borb{\'a}la Kiss and Houtkooper, {Riekelt H.} and Kristina Schoonjans and Val{\'e}rie Schreiber and Sauve, {Anthony A.} and {Menissier-de Murcia}, Josiane and Johan Auwerx",

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doi = "https://doi.org/10.1016/j.cmet.2011.03.004",

language = "English",

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T1 - PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation

AU - Bai, Péter

AU - Cantó, Carles

AU - Oudart, Hugues

AU - Brunyánszki, Attila

AU - Cen, Yana

AU - Thomas, Charles

AU - Yamamoto, Hiroyasu

AU - Huber, Aline

AU - Kiss, Borbála

AU - Houtkooper, Riekelt H.

AU - Schoonjans, Kristina

AU - Schreiber, Valérie

AU - Sauve, Anthony A.

AU - Menissier-de Murcia, Josiane

AU - Auwerx, Johan

PY - 2011

Y1 - 2011

N2 - SIRT1 regulates energy homeostasis by controlling the acetylation status and activity of a number of enzymes and transcriptional regulators. The fact that NAD(+) levels control SIRT1 activity confers a hypothetical basis for the design of new strategies to activate SIRT1 by increasing NAD(+) availability. Here we show that the deletion of the poly(ADP-ribose) polymerase-1 (PARP-1) gene, encoding a major NAD(+)-consuming enzyme, increases NAD(+) content and SIRT1 activity in brown adipose tissue and muscle. PARP-1(-/-) mice phenocopied many aspects of SIRT1 activation, such as a higher mitochondrial content, increased energy expenditure, and protection against metabolic disease. Also, the pharmacologic inhibition of PARP in vitro and in vivo increased NAD(+) content and SIRT1 activity and enhanced oxidative metabolism. These data show how PARP-1 inhibition has strong metabolic implications through the modulation of SIRT1 activity, a property that could be useful in the management not only of metabolic diseases, but also of cancer

AB - SIRT1 regulates energy homeostasis by controlling the acetylation status and activity of a number of enzymes and transcriptional regulators. The fact that NAD(+) levels control SIRT1 activity confers a hypothetical basis for the design of new strategies to activate SIRT1 by increasing NAD(+) availability. Here we show that the deletion of the poly(ADP-ribose) polymerase-1 (PARP-1) gene, encoding a major NAD(+)-consuming enzyme, increases NAD(+) content and SIRT1 activity in brown adipose tissue and muscle. PARP-1(-/-) mice phenocopied many aspects of SIRT1 activation, such as a higher mitochondrial content, increased energy expenditure, and protection against metabolic disease. Also, the pharmacologic inhibition of PARP in vitro and in vivo increased NAD(+) content and SIRT1 activity and enhanced oxidative metabolism. These data show how PARP-1 inhibition has strong metabolic implications through the modulation of SIRT1 activity, a property that could be useful in the management not only of metabolic diseases, but also of cancer

U2 - https://doi.org/10.1016/j.cmet.2011.03.004

DO - https://doi.org/10.1016/j.cmet.2011.03.004

M3 - Article

C2 - 21459330

SN - 1550-4131

VL - 13

SP - 461

EP - 468

JO - Cell metabolism

JF - Cell metabolism

IS - 4

ER -