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Study Reveals Microautophagy Clears Damaged Mitochondria in Macrophages

The pathway shifts immune-cell metabolism toward glycolysis, priming an M1 inflammatory state.

Overview

  • Researchers from the University of Osaka show that lysosome-related organelles directly engulf damaged mitochondria in macrophages, operating independently of macroautophagy.
  • The peer-reviewed study, published August 30, 2025 in Nature Communications (DOI: 10.1038/s41467-025-63531-x), provides live-imaging and genetic evidence for this clearance route.
  • Key regulators of the process include Rab32 GTPase, phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], ubiquitin, and the adaptor protein p62/SQSTM1.
  • In cells exposed to a mitochondria-damaging chemical, the microautophagic mechanism bypassed autophagosomes as damaged organelles were directly sequestered into lysosome-related compartments.
  • Rab32/38 knockout impaired mitochondrial clearance and dampened the linked metabolic and activation changes, and the authors call for further in vivo studies to define the pathway’s broader relevance.