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GET pathway mediates transfer of mislocalized tail-anchored proteins from mitochondria to the ER

Shunsuke Matsumoto1,2,3, Suzuka Ono1,2, Saori Shinoda1

  • 1Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Japan.

The Journal of Cell Biology
|April 20, 2022
PubMed

Insights

Tail-anchored proteins mislocalized to mitochondria are cleared via transfer to the ER. This mitochondria-to-ER transport is Msp1-dependent and facilitated by the GET pathway, ensuring proper protein quality control.

Area of Science:

  • Cell biology
  • Protein trafficking
  • Membrane biology

Background:

  • Tail-anchored (TA) proteins can mislocalize to the mitochondrial outer membrane (OM).
  • Mitochondrial AAA-ATPase Msp1 extracts mislocalized TA proteins from the OM.
  • Extracted TA proteins are transferred to the ER for quality control by the Doa10 complex.

Purpose of the Study:

  • To elucidate the mechanism of TA protein transfer from mitochondria to the ER.
  • To determine if this transfer is essential for clearing mislocalized TA proteins.
  • To investigate the role of the GET pathway in this process.

Main Methods:

  • Time-lapse microscopy to track protein movement.
  • Genetic analysis of Msp1, Doa10, and GET pathway mutants.
  • Observation of authentic ER-TA protein mislocalization.

Main Results:

  • Mislocalized TA proteins move from mitochondria to the ER in an Msp1-dependent manner.
  • This mitochondria-to-ER transfer is blocked by defects in the GET system.
  • The GET pathway facilitates TA protein transfer independently of Doa10 function.

Conclusions:

  • The GET pathway is crucial for facilitating the transfer of mislocalized TA proteins from mitochondria to the ER.
  • This transfer mechanism is essential for the efficient clearance of mislocalized TA proteins.
  • Msp1 and the GET pathway cooperate in managing TA protein quality control.

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