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Updated: Aug 23, 2025

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice
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In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice

Published on: November 22, 2017

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ER-mitochondrial contact protein Miga regulates autophagy through Atg14 and Uvrag

Lingna Xu1, Yunyi Qiu2, Xufeng Wang2

  • 1Department of Obstetrics, Life Sciences Institute, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; MOE Key Laboratory for Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.

Cell Reports
|November 2, 2022
PubMed

Insights

Mitochondrial protein Miga is essential for autophagy, regulating the fusion of autophagosomes and lysosomes. Its absence impairs autophagy by affecting key proteins and lipid production at contact sites.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Molecular Biology

Background:

  • Mitochondrial dysfunction and impaired autophagy are linked to neurodegenerative diseases.
  • Endoplasmic reticulum-mitochondrial contact sites (ERMCSs) play crucial roles in cellular processes.

Purpose of the Study:

  • To investigate the role of Miga, a mitochondrial outer-membrane protein, in regulating autophagy.
  • To elucidate the molecular mechanisms by which Miga influences autophagy and ERMCSs.

Main Methods:

  • Utilized Miga mutants to observe autophagy markers and substrate accumulation.
  • Analyzed the impact of Miga on autophagosome-lysosome fusion and protein recruitment.
  • Investigated Miga's interaction with autophagy-related proteins (Atg14, Uvrag) and PI3K complex components.

Main Results:

  • Loss of Miga leads to defective autophagy, evidenced by accumulating markers and reduced PI3P and Syx17 levels.
  • Miga is required for efficient autophagosome-lysosome fusion.
  • Miga binds to Atg14 and Uvrag, facilitating their recruitment to mitochondria and modulating PI3K activity and Syx17 stabilization.

Conclusions:

  • Miga is a key mitochondrial regulator of autophagy.
  • Miga controls autophagy by orchestrating ERMCSs and recruiting essential PI3K complex components.
  • Miga's function highlights a critical link between mitochondria, ERMCSs, and autophagic processes in cellular health.
Keywords:
CP: Cell biologyDrosophilaER–mitochondrial contactautophagylysosomemitochondria

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