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Oligomer-based functions of mitochondrial porin

Hironori Takeda1,2, Saori Shinoda1,3, Chiho Goto1

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

Nature Communications
|July 27, 2025
PubMed

Insights

Yeast porin (Por1) assembly, beyond its transport role, facilitates mitochondrial protein import, maintains outer membrane lipid composition, and regulates mitochondrial DNA. This study reveals novel functions of this key mitochondrial channel.

Area of Science:

  • Mitochondrial biology
  • Structural biology
  • Molecular and cell biology

Background:

  • Porin, also known as voltage-dependent anion channel (VDAC), is a crucial β-barrel channel in the mitochondrial outer membrane.
  • It is essential for transporting small molecules and ions, and plays significant roles in apoptosis and inflammatory responses.

Purpose of the Study:

  • To determine the high-resolution cryo-electron microscopy structure of yeast porin (Por1) in its hexameric form.
  • To investigate the functions of Por1 assembly beyond its canonical transport role by introducing mutations at protomer interfaces.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine the 3.2 Å resolution structure of hexameric yeast porin (Por1).
  • Site-directed mutagenesis at protomer interfaces to probe Por1 assembly functions.
  • Screening for interacting proteins, including nucleases, using Por1 mutants.

Main Results:

  • The study revealed the hexameric structure of yeast porin (Por1) at 3.2 Å resolution.
  • Mutagenesis identified three critical functions of Por1 assembly: binding unassembled Tom22 to aid mitochondrial protein import, acting as a lipid scramblase for outer membrane lipid homeostasis, and regulating mitochondrial DNA retention and loss.
  • Identification of nucleases cooperating with Por1 in mitochondrial DNA management.

Conclusions:

  • Yeast porin (Por1) assembly has multifaceted roles extending beyond ion and metabolite transport.
  • Por1 is integral to mitochondrial protein import, membrane lipid regulation, and mitochondrial DNA stability.
  • The structural insights and functional characterization of Por1 mutants provide a foundation for further research into mitochondrial dynamics and dysfunction.

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