S-Guanylation proteomics for Redox-based mitochondrial signaling

Md Mizanur Rahaman, Tomohiro Sawa, Ahmed Khandaker Ahtesham, Shahzada Khan, Hirofumi Inoue, Atsuhi Irie, Shigemoto Fujii, Takaaki Akaike

研究成果: Article査読

24 被引用数 (Scopus)

抄録

Aims: 8-nitroguanosine 3′,5′-cyclic monophosphate (8-Nitro-cGMP) is a nitrated derivative of cGMP that is formed via cross-talk of reactive oxygen species formed by NADPH oxidase 2 and mitochondria. This nitrated nucleotide can function as a unique electrophilic second messenger in regulation of redox signaling by inducing a post-translational modification of protein thiols via cGMP adduction (protein S-guanylation). With S-guanylation proteomics, we investigated endogenous mitochondrial protein S-guanylation. Results: We developed a new mass spectrometry (MS)-based proteomic method - S-guanylation proteomics - which comprised two approaches: (i) direct protein digestion followed by immunoaffinity capture of S-guanylated peptides that were subjected to liquid chromatography-tandem MS (LC-MS/MS); and (ii) two-dimensional (2D)-gel electrophoretic separation of S-guanylated proteins that were subjected to in-gel digestion, followed by LC-MS/MS. We thereby identified certain mitochondrial proteins that are S-guanylated endogenously during immunological stimulation, including mortalin and 60-kDa heat-shock protein (HSP60). Mortalin and HSP60 were recently reported to regulate mitochondrial permeability-transition pore (mPTP) opening, at least partly, by interacting with cyclophilin D, an mPTP component. Our data revealed that immunological stimulation and 8-nitro-cGMP treatment induced mPTP opening in a cyclophilin D-dependent manner. Innovation and Conclusion: Our S-guanylation proteomic method determined that mitochondrial HSPs may be novel targets for redox modification via protein S-guanylation that participates in mPTP regulation and mitochondrial redox signaling. Antioxid. Redox Signal. 20, 295-307.

本文言語English
ページ(範囲)295-307
ページ数13
ジャーナルAntioxidants and Redox Signaling
20
2
DOI
出版ステータスPublished - 2014

ASJC Scopus subject areas

  • 生理学
  • 生化学
  • 分子生物学
  • 臨床生化学
  • 細胞生物学

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