Instability in NAD+ metabolism leads to impaired cardiac mitochondrial function and communication

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Instability in NAD+ metabolism leads to impaired cardiac mitochondrial function and communication. / Lauritzen, Knut H.; Olsen, Maria Belland; Ahmed, Mohammed Shakil; Yang, Kuan; Rinholm, Johanne Egge; Bergersen, Linda H.; Esbensen, Qin Ying; Sverkeli, Lars Jansen; Ziegler, Mathias; Attramadal, Havard; Halvorsen, Bente; Aukrust, Pal; Yndestad, Arne.

In: eLife, Vol. 10, 59828, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Lauritzen, KH, Olsen, MB, Ahmed, MS, Yang, K, Rinholm, JE, Bergersen, LH, Esbensen, QY, Sverkeli, LJ, Ziegler, M, Attramadal, H, Halvorsen, B, Aukrust, P & Yndestad, A 2021, 'Instability in NAD+ metabolism leads to impaired cardiac mitochondrial function and communication', eLife, vol. 10, 59828. https://doi.org/10.7554/eLife.59828

APA

Lauritzen, K. H., Olsen, M. B., Ahmed, M. S., Yang, K., Rinholm, J. E., Bergersen, L. H., Esbensen, Q. Y., Sverkeli, L. J., Ziegler, M., Attramadal, H., Halvorsen, B., Aukrust, P., & Yndestad, A. (2021). Instability in NAD+ metabolism leads to impaired cardiac mitochondrial function and communication. eLife, 10, [59828]. https://doi.org/10.7554/eLife.59828

Vancouver

Lauritzen KH, Olsen MB, Ahmed MS, Yang K, Rinholm JE, Bergersen LH et al. Instability in NAD+ metabolism leads to impaired cardiac mitochondrial function and communication. eLife. 2021;10. 59828. https://doi.org/10.7554/eLife.59828

Author

Lauritzen, Knut H. ; Olsen, Maria Belland ; Ahmed, Mohammed Shakil ; Yang, Kuan ; Rinholm, Johanne Egge ; Bergersen, Linda H. ; Esbensen, Qin Ying ; Sverkeli, Lars Jansen ; Ziegler, Mathias ; Attramadal, Havard ; Halvorsen, Bente ; Aukrust, Pal ; Yndestad, Arne. / Instability in NAD+ metabolism leads to impaired cardiac mitochondrial function and communication. In: eLife. 2021 ; Vol. 10.

Bibtex

@article{9c477f9753fc4f2cb005974b55de2ac2,
title = "Instability in NAD+ metabolism leads to impaired cardiac mitochondrial function and communication",
abstract = "Poly(ADP-ribose) polymerase (PARP) enzymes initiate (mt)DNA repair mechanisms and use nicotinamide adenine dinucleotide (NAD(+)) as energy source. Prolonged PARP activity can drain cellular NAD(+) reserves, leading to de-regulation of important molecular processes. Here, we provide evidence of a pathophysiological mechanism that connects mtDNA damage to cardiac dysfunction via reduced NAD(+) levels and loss of mitochondrial function and communication. Using a transgenic model, we demonstrate that high levels of mice cardiomyocyte mtDNA damage cause a reduction in NAD(+) levels due to extreme DNA repair activity, causing impaired activation of NAD(+)- dependent SIRT3. In addition, we show that myocardial mtDNA damage in combination with high dosages of nicotinamideriboside (NR) causes an inhibition of sirtuin activity due to accumulation of nicotinamide (NAM), in addition to irregular cardiac mitochondrial morphology. Consequently, high doses of NR should be used with caution, especially when cardiomyopathic symptoms are caused by mitochondrial dysfunction and instability of mtDNA.",
keywords = "NICOTINAMIDE ADENINE-DINUCLEOTIDE, SIRT3 DEACETYLATES, DOXORUBICIN, TOXICITY, DYNAMICS, DISEASE, REPAIR",
author = "Lauritzen, {Knut H.} and Olsen, {Maria Belland} and Ahmed, {Mohammed Shakil} and Kuan Yang and Rinholm, {Johanne Egge} and Bergersen, {Linda H.} and Esbensen, {Qin Ying} and Sverkeli, {Lars Jansen} and Mathias Ziegler and Havard Attramadal and Bente Halvorsen and Pal Aukrust and Arne Yndestad",
year = "2021",
doi = "10.7554/eLife.59828",
language = "English",
volume = "10",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd.",

}

RIS

TY - JOUR

T1 - Instability in NAD+ metabolism leads to impaired cardiac mitochondrial function and communication

AU - Lauritzen, Knut H.

AU - Olsen, Maria Belland

AU - Ahmed, Mohammed Shakil

AU - Yang, Kuan

AU - Rinholm, Johanne Egge

AU - Bergersen, Linda H.

AU - Esbensen, Qin Ying

AU - Sverkeli, Lars Jansen

AU - Ziegler, Mathias

AU - Attramadal, Havard

AU - Halvorsen, Bente

AU - Aukrust, Pal

AU - Yndestad, Arne

PY - 2021

Y1 - 2021

N2 - Poly(ADP-ribose) polymerase (PARP) enzymes initiate (mt)DNA repair mechanisms and use nicotinamide adenine dinucleotide (NAD(+)) as energy source. Prolonged PARP activity can drain cellular NAD(+) reserves, leading to de-regulation of important molecular processes. Here, we provide evidence of a pathophysiological mechanism that connects mtDNA damage to cardiac dysfunction via reduced NAD(+) levels and loss of mitochondrial function and communication. Using a transgenic model, we demonstrate that high levels of mice cardiomyocyte mtDNA damage cause a reduction in NAD(+) levels due to extreme DNA repair activity, causing impaired activation of NAD(+)- dependent SIRT3. In addition, we show that myocardial mtDNA damage in combination with high dosages of nicotinamideriboside (NR) causes an inhibition of sirtuin activity due to accumulation of nicotinamide (NAM), in addition to irregular cardiac mitochondrial morphology. Consequently, high doses of NR should be used with caution, especially when cardiomyopathic symptoms are caused by mitochondrial dysfunction and instability of mtDNA.

AB - Poly(ADP-ribose) polymerase (PARP) enzymes initiate (mt)DNA repair mechanisms and use nicotinamide adenine dinucleotide (NAD(+)) as energy source. Prolonged PARP activity can drain cellular NAD(+) reserves, leading to de-regulation of important molecular processes. Here, we provide evidence of a pathophysiological mechanism that connects mtDNA damage to cardiac dysfunction via reduced NAD(+) levels and loss of mitochondrial function and communication. Using a transgenic model, we demonstrate that high levels of mice cardiomyocyte mtDNA damage cause a reduction in NAD(+) levels due to extreme DNA repair activity, causing impaired activation of NAD(+)- dependent SIRT3. In addition, we show that myocardial mtDNA damage in combination with high dosages of nicotinamideriboside (NR) causes an inhibition of sirtuin activity due to accumulation of nicotinamide (NAM), in addition to irregular cardiac mitochondrial morphology. Consequently, high doses of NR should be used with caution, especially when cardiomyopathic symptoms are caused by mitochondrial dysfunction and instability of mtDNA.

KW - NICOTINAMIDE ADENINE-DINUCLEOTIDE

KW - SIRT3 DEACETYLATES

KW - DOXORUBICIN

KW - TOXICITY

KW - DYNAMICS

KW - DISEASE

KW - REPAIR

U2 - 10.7554/eLife.59828

DO - 10.7554/eLife.59828

M3 - Journal article

C2 - 34343089

VL - 10

JO - eLife

JF - eLife

SN - 2050-084X

M1 - 59828

ER -

ID: 276156022