Design of novel fluorescent mitochondria-targeted peptides with iron-selective sensing activity

Vincenzo Abbate, Olivier Reelfs, Robert C Hider, Charareh Pourzand

Research output: Contribution to journalArticle

9 Citations (Scopus)
127 Downloads (Pure)

Abstract

Mitochondrial labile iron (LI) plays a crucial role in oxidative injuries and pathologies. At present, there is no organelle-specific sensitive iron sensor which can reside exclusively in the mitochondria and reliably monitor levels of LI in this organelle. Here we describe the development of novel fluorescent and highly specific mitochondria iron sensors, using the family of mitochondrial-homing ‘SS-peptides’ (short cell permeable signal peptides mimicking mitochondrial import sequence) as carriers of highly specific iron chelators for sensitive evaluation of the mitochondrial LI. Microscopy analysis of subcellular localization of a small library of fluorescently labelled SS-like peptides identified dansyl (DNS) as the lead fluorophore for the subsequent synthesis of chimeric iron chelator-peptides of either catechol (compound 10 and 11) or hydroxypyridinone (compounds 13 and 14) type. The iron-sensing ability of these chimeric compounds was confirmed by fluorescent quenching and de-quenching studies both in solution and in cells, with compound 13 exhibiting the highest sensitivity towards iron modulation. The intramolecular fluorophore-chelator distance and the iron affinity both influence probe sensitivity towards iron. These probes represent the first example of highly sensitive mitochondria-directed fluorescent iron chelators with significant potential to monitor mitochondrial LI level.
Original languageEnglish
Pages (from-to)357-366
Number of pages10
JournalBiochemical Journal
Volume469
Issue number3
Early online date26 May 2015
DOIs
Publication statusPublished - 23 Jul 2015

Fingerprint

Mitochondria
Iron
Peptides
Chelating Agents
Fluorophores
Organelles
Quenching
Sensors
Pathology
Protein Sorting Signals
Libraries
Microscopy
Microscopic examination

Cite this

Design of novel fluorescent mitochondria-targeted peptides with iron-selective sensing activity. / Abbate, Vincenzo; Reelfs, Olivier; Hider, Robert C; Pourzand, Charareh.

In: Biochemical Journal, Vol. 469, No. 3, 23.07.2015, p. 357-366.

Research output: Contribution to journalArticle

Abbate, Vincenzo ; Reelfs, Olivier ; Hider, Robert C ; Pourzand, Charareh. / Design of novel fluorescent mitochondria-targeted peptides with iron-selective sensing activity. In: Biochemical Journal. 2015 ; Vol. 469, No. 3. pp. 357-366.
@article{91223cfda6934383b3e4ed7fd62d8ff2,
title = "Design of novel fluorescent mitochondria-targeted peptides with iron-selective sensing activity",
abstract = "Mitochondrial labile iron (LI) plays a crucial role in oxidative injuries and pathologies. At present, there is no organelle-specific sensitive iron sensor which can reside exclusively in the mitochondria and reliably monitor levels of LI in this organelle. Here we describe the development of novel fluorescent and highly specific mitochondria iron sensors, using the family of mitochondrial-homing ‘SS-peptides’ (short cell permeable signal peptides mimicking mitochondrial import sequence) as carriers of highly specific iron chelators for sensitive evaluation of the mitochondrial LI. Microscopy analysis of subcellular localization of a small library of fluorescently labelled SS-like peptides identified dansyl (DNS) as the lead fluorophore for the subsequent synthesis of chimeric iron chelator-peptides of either catechol (compound 10 and 11) or hydroxypyridinone (compounds 13 and 14) type. The iron-sensing ability of these chimeric compounds was confirmed by fluorescent quenching and de-quenching studies both in solution and in cells, with compound 13 exhibiting the highest sensitivity towards iron modulation. The intramolecular fluorophore-chelator distance and the iron affinity both influence probe sensitivity towards iron. These probes represent the first example of highly sensitive mitochondria-directed fluorescent iron chelators with significant potential to monitor mitochondrial LI level.",
author = "Vincenzo Abbate and Olivier Reelfs and Hider, {Robert C} and Charareh Pourzand",
year = "2015",
month = "7",
day = "23",
doi = "10.1042/BJ20150149",
language = "English",
volume = "469",
pages = "357--366",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "3",

}

TY - JOUR

T1 - Design of novel fluorescent mitochondria-targeted peptides with iron-selective sensing activity

AU - Abbate, Vincenzo

AU - Reelfs, Olivier

AU - Hider, Robert C

AU - Pourzand, Charareh

PY - 2015/7/23

Y1 - 2015/7/23

N2 - Mitochondrial labile iron (LI) plays a crucial role in oxidative injuries and pathologies. At present, there is no organelle-specific sensitive iron sensor which can reside exclusively in the mitochondria and reliably monitor levels of LI in this organelle. Here we describe the development of novel fluorescent and highly specific mitochondria iron sensors, using the family of mitochondrial-homing ‘SS-peptides’ (short cell permeable signal peptides mimicking mitochondrial import sequence) as carriers of highly specific iron chelators for sensitive evaluation of the mitochondrial LI. Microscopy analysis of subcellular localization of a small library of fluorescently labelled SS-like peptides identified dansyl (DNS) as the lead fluorophore for the subsequent synthesis of chimeric iron chelator-peptides of either catechol (compound 10 and 11) or hydroxypyridinone (compounds 13 and 14) type. The iron-sensing ability of these chimeric compounds was confirmed by fluorescent quenching and de-quenching studies both in solution and in cells, with compound 13 exhibiting the highest sensitivity towards iron modulation. The intramolecular fluorophore-chelator distance and the iron affinity both influence probe sensitivity towards iron. These probes represent the first example of highly sensitive mitochondria-directed fluorescent iron chelators with significant potential to monitor mitochondrial LI level.

AB - Mitochondrial labile iron (LI) plays a crucial role in oxidative injuries and pathologies. At present, there is no organelle-specific sensitive iron sensor which can reside exclusively in the mitochondria and reliably monitor levels of LI in this organelle. Here we describe the development of novel fluorescent and highly specific mitochondria iron sensors, using the family of mitochondrial-homing ‘SS-peptides’ (short cell permeable signal peptides mimicking mitochondrial import sequence) as carriers of highly specific iron chelators for sensitive evaluation of the mitochondrial LI. Microscopy analysis of subcellular localization of a small library of fluorescently labelled SS-like peptides identified dansyl (DNS) as the lead fluorophore for the subsequent synthesis of chimeric iron chelator-peptides of either catechol (compound 10 and 11) or hydroxypyridinone (compounds 13 and 14) type. The iron-sensing ability of these chimeric compounds was confirmed by fluorescent quenching and de-quenching studies both in solution and in cells, with compound 13 exhibiting the highest sensitivity towards iron modulation. The intramolecular fluorophore-chelator distance and the iron affinity both influence probe sensitivity towards iron. These probes represent the first example of highly sensitive mitochondria-directed fluorescent iron chelators with significant potential to monitor mitochondrial LI level.

U2 - 10.1042/BJ20150149

DO - 10.1042/BJ20150149

M3 - Article

VL - 469

SP - 357

EP - 366

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 3

ER -