Scholarlink

<p>Aurora kinase A/AURKA is a serine/threonine kinase frequently overexpressed in cancer. Recent discoveries pointed to subcellular pools of AURKA, including at mitochondria. There, AURKA induces organelle clearance by mitophagy together with the autophagy mediator LC3, and its receptor PHB2.</p><p>Here, we show that the natural product capsaicin modifies the AURKA/PHB2 interaction. We synthesize 16 capsaicin analogs, and Förster’s Resonance Energy Transfer/Fluorescence Lifetime Imaging Microscopy (FRET/FLIM) in breast cancer cells reveals that compounds <b>12</b> and <b>13</b> increase the AURKA/PHB2 interaction. Molecular docking shows that they bind to the inhibitory pocket of PHB2 and to the AURKA active site. We demonstrate that compound <b>13</b> specifically inhibits mitophagy while leaving AURKA activation unaltered at centrosomes. Our results demonstrate that compound <b>13</b> is a PHB ligand acting on the AURKA/PHB2 interaction. Thanks to its specificity, it may lead to the development of anticancer drugs targeting the mitochondrial functions of AURKA.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Development of capsaicin-derived prohibitin ligands to modulate the Aurora kinase A/PHB2 interaction and mitophagy in cancer cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月24日

查看全文
  • Amel Djehal,
  • Claire Caron,
  • Deborah Giordano,
  • Valentina Pizza,
  • Kimberley Farin,
  • Angelo Facchiano,
  • Laurent Désaubry,
  • Giulia Bertolin

摘要

Aurora kinase A/AURKA is a serine/threonine kinase frequently overexpressed in cancer. Recent discoveries pointed to subcellular pools of AURKA, including at mitochondria. There, AURKA induces organelle clearance by mitophagy together with the autophagy mediator LC3, and its receptor PHB2.

Here, we show that the natural product capsaicin modifies the AURKA/PHB2 interaction. We synthesize 16 capsaicin analogs, and Förster’s Resonance Energy Transfer/Fluorescence Lifetime Imaging Microscopy (FRET/FLIM) in breast cancer cells reveals that compounds 12 and 13 increase the AURKA/PHB2 interaction. Molecular docking shows that they bind to the inhibitory pocket of PHB2 and to the AURKA active site. We demonstrate that compound 13 specifically inhibits mitophagy while leaving AURKA activation unaltered at centrosomes. Our results demonstrate that compound 13 is a PHB ligand acting on the AURKA/PHB2 interaction. Thanks to its specificity, it may lead to the development of anticancer drugs targeting the mitochondrial functions of AURKA.