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Updated: Sep 9, 2025

Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome
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Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome

Published on: November 30, 2022

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Evidence that mitochondria in macrophages are destroyed by microautophagy

Shiou-Ling Lu1, Siyu Chen1, Kazuya Noda1,2

  • 1Department of Oral Cellular Biology, Center for Frontier Oral Science, Graduate School of Dentistry, The University of Osaka, Osaka, Japan.

Nature Communications
|August 30, 2025
PubMed

Insights

Microautophagy directly degrades organelles like mitochondria within macrophages via Rab32-positive organelles. This process is crucial for macrophage M1 polarization and metabolic reprogramming.

Area of Science:

  • Cell Biology
  • Immunology
  • Molecular Biology

Background:

  • Microautophagy is a cellular degradation pathway where lysosomes engulf substrates.
  • Lysosome-related organelles (LROs) play diverse roles in cellular processes.
  • Macrophage polarization is critical for immune responses and metabolic homeostasis.

Purpose of the Study:

  • To investigate the role of Rab32-positive LROs in cellular degradation within macrophages.
  • To elucidate the mechanism of organelle engulfment by LROs, independent of other degradation pathways.
  • To determine the impact of this degradation process on macrophage polarization and function.

Main Methods:

  • Utilized cell culture models of macrophages.
  • Investigated organelle engulfment using microscopy and biochemical assays.
  • Examined the role of Rab32, phosphatidylinositol 3,5-bisphosphates, ubiquitination, and p62/SQSTM1.
  • Assessed macrophage M1 polarization and metabolic changes in wild-type and Rab32/38 double-knockout macrophages.

Main Results:

  • Rab32-positive LROs directly engulf organelles, including mitochondria and endosomes, via membrane invagination/protrusion.
  • Mitochondrial degradation occurs independently of macroautophagy and ESCRT machinery.
  • Rab32 GTPase, PI(3,5)P2, ubiquitination, and p62/SQSTM1 are essential for this microautophagy pathway.
  • Elimination of mitochondria via this pathway promotes metabolic reprogramming towards glycolysis.
  • M1 polarization of macrophages is significantly impaired in Rab32/38 double-knockout cells.

Conclusions:

  • Microautophagy mediated by Rab32-positive LROs is a novel mechanism for organelle degradation in macrophages.
  • This pathway is critical for regulating macrophage metabolism and M1 polarization.
  • The findings reveal a new role for microautophagy in immune cell physiology.

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