Nitration of specific tyrosines in FoF1 ATP synthase and activity loss in aging

Virginia Haynes, Nathaniel Traaseth, Sarah Elfering, Yasuko Fujisawa, Cecilia Giulivi

Research output: Contribution to journalArticle

Abstract

It has been reported that C-nitration of proteins occurs under nitrative/oxidative stress; however, its role in pathophysiological situations is not fully understood. In this study, we determined that nitration of Tyr 345 and Tyr368 in the β-subunit of the mitochondrial FoF1-ATPase is a major target for nitrative stress in rat liver under in vivo conditions. The chemical characteristics of these Tyr make them suitable for a facilitated nitration (solvent accessibility, consensus sequence, and pKa). Moreover, β-subunit nitration increased significantly with the age of the rats (from 4 to 80 weeks old) and correlated with decreased ATP hydrolysis and synthesis rates. Although its affinity for ATP binding was unchanged, maximal ATPase activity decreased between young and old rats by a factor of two. These changes directly impacted the available ATP concentration in vivo, and it was expected that they would affect multiple cellular ATP-dependent processes. For instance, at least 50% of available [ATP] in the liver of older rats would have to be committed to sustain maximal Na +-K+-ATPase activity, whereas only 30% would be required for young rats. If this requirement was not fulfilled, the osmoregulation and Na+-nutrient cotransport in liver of older rats would be compromised. On the basis of our studies, we propose that targeted nitration of the β-subunit is an early marker for nitrative stress and aging.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume298
Issue number5
DOIs
StatePublished - May 2010

Fingerprint

Tyrosine
Adenosine Triphosphate
Adenosine Triphosphatases
Liver
Osmoregulation
Consensus Sequence
Protein C
Oxidative Stress
Hydrolysis
Food

Keywords

  • Adenosine 5′-triphosphatase
  • Adenosine 5′-triphosphate
  • Bioenergetics
  • Biomarker
  • Mitochondria

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Nitration of specific tyrosines in FoF1 ATP synthase and activity loss in aging. / Haynes, Virginia; Traaseth, Nathaniel; Elfering, Sarah; Fujisawa, Yasuko; Giulivi, Cecilia.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 298, No. 5, 05.2010.

Research output: Contribution to journalArticle

@article{732dc1b48a5543098feee8391ea68542,
title = "Nitration of specific tyrosines in FoF1 ATP synthase and activity loss in aging",
abstract = "It has been reported that C-nitration of proteins occurs under nitrative/oxidative stress; however, its role in pathophysiological situations is not fully understood. In this study, we determined that nitration of Tyr 345 and Tyr368 in the β-subunit of the mitochondrial FoF1-ATPase is a major target for nitrative stress in rat liver under in vivo conditions. The chemical characteristics of these Tyr make them suitable for a facilitated nitration (solvent accessibility, consensus sequence, and pKa). Moreover, β-subunit nitration increased significantly with the age of the rats (from 4 to 80 weeks old) and correlated with decreased ATP hydrolysis and synthesis rates. Although its affinity for ATP binding was unchanged, maximal ATPase activity decreased between young and old rats by a factor of two. These changes directly impacted the available ATP concentration in vivo, and it was expected that they would affect multiple cellular ATP-dependent processes. For instance, at least 50{\%} of available [ATP] in the liver of older rats would have to be committed to sustain maximal Na +-K+-ATPase activity, whereas only 30{\%} would be required for young rats. If this requirement was not fulfilled, the osmoregulation and Na+-nutrient cotransport in liver of older rats would be compromised. On the basis of our studies, we propose that targeted nitration of the β-subunit is an early marker for nitrative stress and aging.",
keywords = "Adenosine 5′-triphosphatase, Adenosine 5′-triphosphate, Bioenergetics, Biomarker, Mitochondria",
author = "Virginia Haynes and Nathaniel Traaseth and Sarah Elfering and Yasuko Fujisawa and Cecilia Giulivi",
year = "2010",
month = "5",
doi = "10.1152/ajpendo.00739.2009",
language = "English (US)",
volume = "298",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "5",

}

TY - JOUR

T1 - Nitration of specific tyrosines in FoF1 ATP synthase and activity loss in aging

AU - Haynes, Virginia

AU - Traaseth, Nathaniel

AU - Elfering, Sarah

AU - Fujisawa, Yasuko

AU - Giulivi, Cecilia

PY - 2010/5

Y1 - 2010/5

N2 - It has been reported that C-nitration of proteins occurs under nitrative/oxidative stress; however, its role in pathophysiological situations is not fully understood. In this study, we determined that nitration of Tyr 345 and Tyr368 in the β-subunit of the mitochondrial FoF1-ATPase is a major target for nitrative stress in rat liver under in vivo conditions. The chemical characteristics of these Tyr make them suitable for a facilitated nitration (solvent accessibility, consensus sequence, and pKa). Moreover, β-subunit nitration increased significantly with the age of the rats (from 4 to 80 weeks old) and correlated with decreased ATP hydrolysis and synthesis rates. Although its affinity for ATP binding was unchanged, maximal ATPase activity decreased between young and old rats by a factor of two. These changes directly impacted the available ATP concentration in vivo, and it was expected that they would affect multiple cellular ATP-dependent processes. For instance, at least 50% of available [ATP] in the liver of older rats would have to be committed to sustain maximal Na +-K+-ATPase activity, whereas only 30% would be required for young rats. If this requirement was not fulfilled, the osmoregulation and Na+-nutrient cotransport in liver of older rats would be compromised. On the basis of our studies, we propose that targeted nitration of the β-subunit is an early marker for nitrative stress and aging.

AB - It has been reported that C-nitration of proteins occurs under nitrative/oxidative stress; however, its role in pathophysiological situations is not fully understood. In this study, we determined that nitration of Tyr 345 and Tyr368 in the β-subunit of the mitochondrial FoF1-ATPase is a major target for nitrative stress in rat liver under in vivo conditions. The chemical characteristics of these Tyr make them suitable for a facilitated nitration (solvent accessibility, consensus sequence, and pKa). Moreover, β-subunit nitration increased significantly with the age of the rats (from 4 to 80 weeks old) and correlated with decreased ATP hydrolysis and synthesis rates. Although its affinity for ATP binding was unchanged, maximal ATPase activity decreased between young and old rats by a factor of two. These changes directly impacted the available ATP concentration in vivo, and it was expected that they would affect multiple cellular ATP-dependent processes. For instance, at least 50% of available [ATP] in the liver of older rats would have to be committed to sustain maximal Na +-K+-ATPase activity, whereas only 30% would be required for young rats. If this requirement was not fulfilled, the osmoregulation and Na+-nutrient cotransport in liver of older rats would be compromised. On the basis of our studies, we propose that targeted nitration of the β-subunit is an early marker for nitrative stress and aging.

KW - Adenosine 5′-triphosphatase

KW - Adenosine 5′-triphosphate

KW - Bioenergetics

KW - Biomarker

KW - Mitochondria

UR - http://www.scopus.com/inward/record.url?scp=77950815689&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950815689&partnerID=8YFLogxK

U2 - 10.1152/ajpendo.00739.2009

DO - 10.1152/ajpendo.00739.2009

M3 - Article

VL - 298

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 5

ER -