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  3. Molecular Imaging of Labile Heme in Living Cells Using a Small Molecule Fluorescent Probe

Molecular Imaging of Labile Heme in Living Cells Using a Small Molecule Fluorescent Probe

  • J Am Chem Soc. 2022 Mar 9;144(9):3793-3803. doi: 10.1021/jacs.1c08485.
Kanta Kawai 1,  Tasuku Hirayama 1,  Haruka Imai 1,  Takanori Murakami 2,  Masatoshi Inden 2,  Isao Hozumi 2,  Hideko Nagasawa 1
Affiliations

Affiliations

  • 1 Laboratory of Pharmaceutical and Medicinal Chemistry, Gifu Pharmaceutical University, Gifu-shi, Gifu 501-1196, Japan.
  • 2 Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, Gifu-shi, Gifu 501-1196, Japan.
PMID: 35133144 DOI: 10.1021/jacs.1c08485
Abstract

Labile heme (LH) is a complex of Fe(II) and protoporphyrin IX, an essential signaling molecule in various biological systems. Most of the subcellular dynamics of LH remain unclear because of the lack of efficient chemical tools for detecting LH in cells. Here, we report an activity-based fluorescence probe that can monitor the fluctuations of LH in biological events. H-FluNox is a selective fluorescent probe that senses LH using biomimetic N-oxide deoxygenation to trigger fluorescence. The selectivity of H-FluNox to LH is >100-fold against Fe(II), enabling the discrimination of LH from the labile Fe(II) pool in living cells. The probe can detect the acute release of LH upon NO stimulation and the accumulation of LH by inhibiting the heme exporter. In addition, imaging studies using the probe revealed a partial heme-export activity of the ATP-binding cassette subfamily G member 2 (ABCG2), potential LH pooling ability of G-quadruplex, and involvement of LH in Ferroptosis. The successful use of H-FluNox in identifying fluctuations of LH in living cells offers opportunities for studying the physiology and pathophysiology of LH in living systems.

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