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Updated: Sep 14, 2025

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MITF promotes MFN2-dependent mitochondrial fusion to protect retinal pigment epithelial cells from mitochondrial

Ying-Ao Chen1, Wan-Ni Lu1, Pingping Li1

  • 1Laboratory of Developmental Cell Biology and Disease, State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.

Free Radical Biology & Medicine
|July 18, 2025
PubMed

Insights

Protecting retinal pigment epithelium (RPE) involves boosting mitochondrial fusion. Microphthalmia-associated transcription factor (MITF) promotes fusion and protects RPE cells from damage, offering new therapeutic insights.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Mitochondrial Biology

Background:

  • Retinal pigment epithelium (RPE) dysfunction and degeneration are linked to mitochondrial damage.
  • The molecular mechanisms underlying RPE protection against mitochondrial damage are not fully understood.

Purpose of the Study:

  • To investigate the role of microphthalmia-associated transcription factor (MITF) in RPE mitochondrial health.
  • To elucidate the mechanisms by which MITF protects RPE cells from mitochondrial damage.

Main Methods:

  • Ex vivo studies using ARPE-19 and mouse primary RPE cells.
  • In vivo studies using Mitf heterozygous, Mitf-overexpressing transgenic, and AAV-mediated MITF overexpression mice.
  • Investigated MITF binding to the Mitofusin 2 (MFN2) promoter.
  • MFN2 knockdown experiments.
  • Mitochondria-targeted SkQ-1 nanoparticle administration.

Main Results:

  • MITF promotes mitochondrial fusion in RPE cells.
  • MITF protects RPE cells from carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced mitochondrial damage.
  • MITF directly activates MFN2 transcription by binding to its promoter.
  • MFN2 knockdown abrogated MITF's protective effects.
  • SkQ-1 nanoparticles protected RPE cells in vivo.

Conclusions:

  • MITF plays a critical role in regulating mitochondrial fusion in RPE cells.
  • MITF-mediated mitochondrial fusion is a key mechanism for protecting RPE against damage.
  • Findings offer insights into RPE abnormalities and retinal degeneration associated with MITF deficiency.
Keywords:
MITFMitochondriaMitochondrial fusionRPERetinal degeneration

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