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<p>Mitochondria constitute vital organelles in eukaryotic cells, essential not only for adenosine triphosphate (ATP) synthesis but also for diverse cellular functions underpinned by their distinctive double-membrane architecture. A comprehensive analysis of the molecular composition and spatial organization of mitochondria, combined with real-time monitoring of intracellular dynamics, enables the systematic elucidation of their operational mechanisms. This necessitates advanced molecular tools, such as small-molecule fluorescent probes, which leverage their low molecular weight to enhance cell permeability and broaden their applicability across cell types. Traditional mitochondria probes typically employ delocalized lipophilic cations, like triphenylphosphonium, but have limitations regarding intracellular accumulation and specificity. To address this issue, an innovative strategy was employed that increases the charge number while incorporating electrostatic interactions and lipid-tail anchoring, yielding the PHPY-C10 probe that achieves exclusive mitochondrial targeting without significant off-organelle accumulation. PHPY-C10 facilitates the real-time tracking of mitochondrial dynamics in stimulated HeLa cells, demonstrating its strong potential for the precise visualization of tumour cell mitochondria and its applications in diagnosing mitochondrial-associated diseases.</p>

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Cell-Permeable Mitochondrial-Targeting Probes Enable Precise Tracking Via the Interplay between Electrostatic Interaction and Lipid-Tail Anchoring Mechanism

  • 期刊论文

  • 发表日期：

    2026年4月29日

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  • Jiaqi Zuo,
  • Longjie Du,
  • Qisheng Zhang,
  • Jianjian Zhou,
  • Jiajia Liao,
  • Weidong Liu,
  • Hui Feng,
  • Jin Zhou,
  • Zhaosheng Qian

摘要

Mitochondria constitute vital organelles in eukaryotic cells, essential not only for adenosine triphosphate (ATP) synthesis but also for diverse cellular functions underpinned by their distinctive double-membrane architecture. A comprehensive analysis of the molecular composition and spatial organization of mitochondria, combined with real-time monitoring of intracellular dynamics, enables the systematic elucidation of their operational mechanisms. This necessitates advanced molecular tools, such as small-molecule fluorescent probes, which leverage their low molecular weight to enhance cell permeability and broaden their applicability across cell types. Traditional mitochondria probes typically employ delocalized lipophilic cations, like triphenylphosphonium, but have limitations regarding intracellular accumulation and specificity. To address this issue, an innovative strategy was employed that increases the charge number while incorporating electrostatic interactions and lipid-tail anchoring, yielding the PHPY-C10 probe that achieves exclusive mitochondrial targeting without significant off-organelle accumulation. PHPY-C10 facilitates the real-time tracking of mitochondrial dynamics in stimulated HeLa cells, demonstrating its strong potential for the precise visualization of tumour cell mitochondria and its applications in diagnosing mitochondrial-associated diseases.