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Msp1 cooperates with the proteasome for extraction of arrested mitochondrial import intermediates

Marion Basch1, Mirjam Wagner1, Stéphane Rolland1

  • 1Zell- und Entwicklungsbiologie, Department Biologie II, Ludwig-Maximilians-Universität München, Planegg-Martinsried 82152, Germany.

Molecular Biology of the Cell
|February 13, 2020
PubMed

Insights

Mitochondrial AAA ATPase Msp1 acts with the proteasome to remove stalled protein precursors at the mitochondrial outer membrane. This interaction is crucial for protein import and suggests a conserved role in metazoan cellular stress responses.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Protein Degradation

Background:

  • Mitochondrial AAA ATPase Msp1 extracts mislocalized tail-anchored ER proteins.
  • Protein import into mitochondria involves the TOM complex translocase.

Purpose of the Study:

  • To investigate the role of Msp1 in extracting protein precursors that block the mitochondrial outer membrane import pore.
  • To elucidate the relationship between Msp1, the proteasome, and the TOM complex in protein import.

Main Methods:

  • Genetic interaction studies involving Msp1, proteasome components, and TOM complex members.
  • Analysis of arrested precursor protein accumulation in mutant strains.
  • Proteasome inhibition assays.
  • Co-purification of Msp1 with the proteasomal subunit Rpn10.
  • Observation of import stress response in *Caenorhabditis elegans* lacking Msp1 homologue.

Main Results:

  • Msp1 and the proteasome genetically interact with TOM complex components.
  • Both Msp1 and the proteasome are required for removing arrested precursor proteins.
  • Proteasome inhibition blocks the extraction of these arrested precursors.
  • The proteasomal subunit Rpn10 was found to co-purify with Msp1.
  • Loss of Msp1 homologue in *C. elegans* triggers an import stress response.

Conclusions:

  • Msp1 functions as an adaptor for the proteasome to extract arrested and mislocalized proteins from the mitochondrial outer membrane.
  • This mechanism highlights a conserved role for Msp1 in metazoan protein import quality control and stress response.

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