Protein targets for carbonylation by 4-hydroxy-2-nonenal in rat liver mitochondria

Jia Guo, Katalin Prokai-Tatrai, Vien Nguyen, Navin Rauniyar, Bettina Ughy, Laszlo Prokai

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Protein carbonylation has been associated with various pathophysiological processes. A representative reactive carbonyl species (RCS), 4-hydroxy-2-nonenal (HNE), has been implicated specifically as a causative factor for the initiation and/or progression of various diseases. To date, however, little is known about the proteins and their modification sites susceptible to "carbonyl stress" by this RCS, especially in the liver. Using chemoprecipitation based on a solid-phase hydrazine chemistry coupled with LC-MS/MS bottom-up approach and database searching, we identified several protein-HNE adducts in isolated rat liver mitochondria upon HNE exposure. The identification of selected major protein targets, such as the ATP synthase β-subunit, was further confirmed by immunoblotting and a gel-based approach in combination with LC-MS/MS. A network was also created based on the identified protein targets, which showed that the main protein interactions were associated with cell death, tumor morphology and drug metabolism, implicating the toxic nature of HNE in the liver mitoproteome. The functional consequence of carbonylation was illustrated by its detrimental impact on the activity of ATP synthase, a representative major mitochondrial protein target for HNE modifications.

Original languageEnglish
Pages (from-to)2370-2379
Number of pages10
JournalJournal of Proteomics
Volume74
Issue number11
DOIs
StatePublished - 19 Oct 2011

Fingerprint

Protein Carbonylation
Carbonylation
Mitochondria
Liver Mitochondrion
Liver
Rats
hydrazine
Proteins
Adenosine Triphosphate
Peptide Initiation Factors
Poisons
Mitochondrial Proteins
Immunoblotting
Cell death
Disease Progression
Metabolism
Cell Death
Gels
4-hydroxy-2-nonenal
Tumors

Keywords

  • 4-Hydroxy-2-nonenal
  • ATP synthase
  • Liver
  • Mitochondria
  • Protein carbonylation
  • Redox proteomics

Cite this

Guo, Jia ; Prokai-Tatrai, Katalin ; Nguyen, Vien ; Rauniyar, Navin ; Ughy, Bettina ; Prokai, Laszlo. / Protein targets for carbonylation by 4-hydroxy-2-nonenal in rat liver mitochondria. In: Journal of Proteomics. 2011 ; Vol. 74, No. 11. pp. 2370-2379.
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Protein targets for carbonylation by 4-hydroxy-2-nonenal in rat liver mitochondria. / Guo, Jia; Prokai-Tatrai, Katalin; Nguyen, Vien; Rauniyar, Navin; Ughy, Bettina; Prokai, Laszlo.

In: Journal of Proteomics, Vol. 74, No. 11, 19.10.2011, p. 2370-2379.

Research output: Contribution to journalArticle

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