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Mitochondria and peroxisomes are NIXed for clearance

Chunxin Wang1, Richard Youle1

  • 1Biochemistry Section, NINDS, NIH, Bethesda, MD, USA.

The EMBO Journal
|November 17, 2022
PubMed

Insights

The iron chelator DFP triggers mitophagy and pexophagy. The mitophagy receptor NIX also functions in peroxisomes to drive pexophagy, revealing a new role for this protein.

Area of Science:

  • Cellular Biology
  • Autophagy Research
  • Organelle Quality Control

Background:

  • Mitophagy and pexophagy are crucial cellular processes for removing damaged mitochondria and peroxisomes, respectively.
  • BNIP3/NIX is a known regulator of mitophagy.
  • The precise mechanisms regulating pexophagy are less understood.

Purpose of the Study:

  • To investigate the role of the iron chelator DFP in inducing mitophagy and pexophagy.
  • To explore the function of BNIP3/NIX in pexophagy.
  • To elucidate the novel functions of NIX beyond mitophagy.

Main Methods:

  • Treatment of cells with DFP.
  • Confocal microscopy to visualize mitophagy and pexophagy.
  • Immunoblotting to assess protein levels.
  • Genetic manipulation to study BNIP3/NIX function.

Main Results:

  • DFP treatment robustly induced both mitophagy and pexophagy.
  • This induction was dependent on BNIP3/NIX.
  • NIX was found to localize to peroxisomes, independent of its role in mitochondria.
  • NIX directly promoted pexophagy in various physiological conditions.

Conclusions:

  • DFP is a potent inducer of both mitophagy and pexophagy via BNIP3/NIX.
  • NIX possesses a dual role, acting as both a mitophagy and a pexophagy receptor.
  • The peroxisomal localization of NIX highlights a novel function with physiological relevance.

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