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Msp1 and Pex19-Pex3 cooperate to achieve correct localization of Pex15 to peroxisomes

Shunsuke Matsumoto1, Yoshiki Kogure1, Suzuka Ono2,3

  • 1Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, Japan.

The FEBS Journal
|May 9, 2025
PubMed

Insights

Yeast Msp1 AAA-ATPase extracts mistargeted tail-anchored proteins from mitochondria and peroxisomes. It re-routes Pex15 to peroxisomes via Pex19-Pex3, ensuring correct localization.

Area of Science:

  • Cell Biology
  • Protein Trafficking
  • Organelle Biogenesis

Background:

  • Yeast Msp1 is a dual-localized AAA-ATPase found on mitochondrial and peroxisomal membranes.
  • Msp1 facilitates the transfer of mistargeted tail-anchored (TA) proteins from mitochondria to the endoplasmic reticulum (ER) for degradation or proper localization.
  • The precise role of Msp1 in handling authentic peroxisomal TA proteins, like Pex15, was previously unclear.

Purpose of the Study:

  • To elucidate the mechanism by which Msp1 in mitochondria and peroxisomes manages authentic peroxisomal TA proteins.
  • To investigate the role of Msp1 in the localization and maintenance of Pex15, a key peroxisomal TA protein.

Main Methods:

  • Utilized yeast genetics and cell biology techniques to track Pex15 localization.
  • Investigated the interactions between Msp1, Pex15, Pex19, and Pex3.
  • Observed the fate of mistargeted and correctly localized Pex15 in the presence and absence of Msp1.

Main Results:

  • Newly synthesized Pex15 is primarily targeted to peroxisomes through the Pex19- and Pex3-dependent pathway.
  • Mitochondrial Msp1 extracts mistargeted Pex15 from the mitochondrial outer membrane (OM) and directs it to the ER for degradation or to peroxisomes.
  • Peroxisomal Msp1 extracts endogenous Pex15 from peroxisomal membranes, which then returns to peroxisomes via the Pex19-Pex3 pathway.

Conclusions:

  • Correct Pex15 localization to peroxisomes depends on the initial Pex19-Pex3 targeting pathway.
  • Msp1 plays a crucial role in the continuous re-routing and maintenance of Pex15 at peroxisomes, even for correctly localized proteins.
  • This study reveals a dynamic quality control mechanism involving Msp1 for peroxisomal TA protein localization.
Keywords:
Msp1Pex15Pex19‐Pex3mitochondriaperoxisome

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