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Updated: Nov 8, 2025

Visualization and Quantification of Endogenous Intra-Organelle Protein Interactions at ER-Mitochondria Contact Sites by Proximity Ligation Assays
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Visualization and Quantification of Endogenous Intra-Organelle Protein Interactions at ER-Mitochondria Contact Sites by Proximity Ligation Assays

Published on: October 20, 2023

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VPS13D bridges the ER to mitochondria and peroxisomes via Miro

Andrés Guillén-Samander1, Marianna Leonzino1, Michael G Hanna1

  • 1Departments of Neuroscience and of Cell Biology, Howard Hughes Medical Institute, Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT.

The Journal of Cell Biology
|April 23, 2021
PubMed

Insights

Mitochondria rely on the ER for lipids. Miro protein recruits VPS13D, creating a lipid transport pathway between the ER and mitochondria, potentially impacting Parkinson's disease.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Neuroscience

Background:

  • Mitochondria require lipids synthesized in the endoplasmic reticulum (ER) and rely on lipid transport proteins for this supply.
  • The ER-mitochondria tethering complex ERMES, with GTPase Gem1, facilitates lipid transfer in yeast.
  • In metazoa, Gem1's orthologue, Miro, is linked to mitochondrial dynamics but not lipid transport, despite the presence of VPS13.

Purpose of the Study:

  • To investigate the role of Miro in lipid transport between the ER and mitochondria in metazoa.
  • To elucidate the molecular mechanism connecting Miro to lipid transfer pathways.
  • To explore potential implications for neurodegenerative diseases like Parkinson's disease.

Main Methods:

  • Utilized yeast genetics and cell biology techniques.
  • Investigated protein-protein interactions involving Miro and VPS13D.
  • Examined ER-mitochondria contact sites and lipid transfer dynamics.

Main Results:

  • Miro, including its peroxisome-enriched splice variant, recruits the lipid transport protein VPS13D.
  • VPS13D binds to the ER in a VAP-dependent manner, establishing a lipid conduit.
  • This pathway provides a functional link between Gem1/Miro functions in yeast and metazoa.

Conclusions:

  • Miro acts as a crucial link for ER-mitochondria lipid transport in metazoa via VPS13D.
  • This mechanism highlights a conserved role for Miro in organelle lipid homeostasis.
  • Findings suggest potential therapeutic targets for Parkinson's disease by modulating this lipid transport pathway.

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