An ATG16L1-dependent pathway promotes plasma membrane repair and limits Listeria monocytogenes cell-to-cell spread

Nat Microbiol. 2018 Dec;3(12):1472-1485. doi: 10.1038/s41564-018-0293-5. Epub 2018 Nov 26.


Plasma membrane integrity is essential for the viability of eukaryotic cells. In response to bacterial pore-forming toxins, disrupted regions of the membrane are rapidly repaired. However, the pathways that mediate plasma membrane repair are unclear. Here we show that autophagy-related (ATG) protein ATG16L1 and its binding partners ATG5 and ATG12 are required for plasma membrane repair through a pathway independent of macroautophagy. ATG16L1 is required for lysosome fusion with the plasma membrane and blebbing responses that promote membrane repair. ATG16L1 deficiency causes accumulation of cholesterol in lysosomes that contributes to defective membrane repair. Cell-to-cell spread by Listeria monocytogenes requires membrane damage by the bacterial toxin listeriolysin O, which is restricted by ATG16L1-dependent membrane repair. Cells harbouring the ATG16L1 T300A allele associated with inflammatory bowel disease were also found to accumulate cholesterol and be defective in repair, linking a common inflammatory disease to plasma membrane integrity. Thus, plasma membrane repair could be an important therapeutic target for the treatment of bacterial infections and inflammatory disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy
  • Autophagy-Related Protein 12 / metabolism
  • Autophagy-Related Protein 5 / metabolism
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism*
  • Autophagy-Related Proteins / pharmacology*
  • Bacterial Toxins / toxicity
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Carrier Proteins / pharmacology
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism*
  • Cholesterol / metabolism
  • Disease Models, Animal
  • Exocytosis
  • HeLa Cells
  • Heat-Shock Proteins / toxicity
  • Hemolysin Proteins / toxicity
  • Humans
  • Listeria monocytogenes / drug effects*
  • Listeria monocytogenes / metabolism
  • Lysosomes
  • Male
  • Mice


  • ATG12 protein, human
  • ATG16L1 protein, human
  • ATG5 protein, human
  • Atg16l1 protein, mouse
  • Autophagy-Related Protein 12
  • Autophagy-Related Protein 5
  • Autophagy-Related Proteins
  • Bacterial Toxins
  • Carrier Proteins
  • Heat-Shock Proteins
  • Hemolysin Proteins
  • Cholesterol
  • hlyA protein, Listeria monocytogenes