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<p>Acute kidney injury (AKI) is a common clinical disease with complex pathophysiological processes and with high morbidity and mortality. Severe mitochondrial damages, such as mitochondrial swelling and fragmentation, disruption of membrane integrity, and broken or absent cristae, were observed in renal tubular epithelial cells (TECs) of ischemic AKI mice. However, whether artificial activation of mitophagy can alleviate TECs injury is still unknown. In this study, we tested the pro-mitophagy effect of UMI-77, which was identified as an unexpected mitophagy activator at sub-lethal doses in 2020, and verified the protective effect of activated mitophagy on TECs during AKI. We found that UMI-77 activates mitophagy in TECs and ameliorates kidney damage during AKI both in vivo and in vitro. This protective effect of UMI-77 on TECs can be reversed by adding mitophagy inhibitor Mdivi-1 or inhibiting the expression of mitophagy receptor MCL-1. These results indicate that UMI-77 mitigates TECs injury in AKI primarily through activating mitophagy, and artificial activation of mitophagy could be an effective strategy for treating AKI.</p>

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Targeting MCL1 by UMI-77 to induce mitophagy alleviates renal tubular epithelial cells injury in acute kidney injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月29日

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  • Xiaoyu Li,
  • Zixian Li,
  • Yongming Chen,
  • Hongluan Wu,
  • Yonghan Liu,
  • Zhennan Ye,
  • Qingqing Yang,
  • Haicha Hou,
  • Junfeng Hao,
  • Ruigao Song,
  • Huafeng Liu

摘要

Acute kidney injury (AKI) is a common clinical disease with complex pathophysiological processes and with high morbidity and mortality. Severe mitochondrial damages, such as mitochondrial swelling and fragmentation, disruption of membrane integrity, and broken or absent cristae, were observed in renal tubular epithelial cells (TECs) of ischemic AKI mice. However, whether artificial activation of mitophagy can alleviate TECs injury is still unknown. In this study, we tested the pro-mitophagy effect of UMI-77, which was identified as an unexpected mitophagy activator at sub-lethal doses in 2020, and verified the protective effect of activated mitophagy on TECs during AKI. We found that UMI-77 activates mitophagy in TECs and ameliorates kidney damage during AKI both in vivo and in vitro. This protective effect of UMI-77 on TECs can be reversed by adding mitophagy inhibitor Mdivi-1 or inhibiting the expression of mitophagy receptor MCL-1. These results indicate that UMI-77 mitigates TECs injury in AKI primarily through activating mitophagy, and artificial activation of mitophagy could be an effective strategy for treating AKI.