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The inhibition of the mitochondrial F1FO-ATPase activity when activated by Ca2+ opens new regulatory roles for NAD+

  • Salvatore Nesci ORCID logo , Fabiana Trombetti , Vittoria Ventrella , Maurizio Pirini and Alessandra Pagliarani ORCID logo EMAIL logo
Published/Copyright: January 10, 2018
Biological Chemistry
From the journal Biological Chemistry Volume 399 Issue 2

Abstract

The mitochondrial F1FO-ATPase is uncompetitively inhibited by NAD+ only when the natural cofactor Mg2+ is replaced by Ca2+, a mode putatively involved in cell death. The Ca2+-dependent F1FO-ATPase is also inhibited when NAD+ concentration in mitochondria is raised by acetoacetate. The enzyme inhibition by NAD+ cannot be ascribed to any de-ac(et)ylation or ADP-ribosylation by sirtuines, as it is not reversed by nicotinamide. Moreover, the addition of acetyl-CoA or palmitate, which would favor the enzyme ac(et)ylation, does not affect the F1FO-ATPase activity. Consistently, NAD+ may play a new role, not associated with redox and non-redox enzymatic reactions, in the Ca2+-dependent regulation of the F1FO-ATPase activity.

Keywords: Ca2+ cofactor; F1FO-ATPase; mitochondria; NAD+

Acknowledgments

Danilo Matteuzzi (DIMEVET, University of Bologna, Italy) is gratefully acknowledged for kindly conferring swine hearts from a local abattoir to our lab. This work was financed by a RFO grant from the University of Bologna, Italy.

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Supplemental Material:

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2017-0209).

Received: 2017-7-25
Accepted: 2017-9-21
Published Online: 2018-1-10
Published in Print: 2018-1-26

©2018 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/hsz-2017-0209
Keywords for this article
Ca2+ cofactor; F1FO-ATPase; mitochondria; NAD+

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Structure and function of the human parvulins Pin1 and Par14/17
  4. Structural mechanisms of HECT-type ubiquitin ligases
  5. Mechanisms, pathophysiological roles and methods for analyzing mitophagy – recent insights
  6. Minireview
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  8. Research Articles/Short Communications
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  10. The dinoponeratoxin peptides from the giant ant Dinoponera quadriceps display in vitro antitrypanosomal activity
  11. The inhibition of the mitochondrial F1FO-ATPase activity when activated by Ca2+ opens new regulatory roles for NAD+
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