Mitochondria shed their outer membrane in response to infection-induced stress

Science. 2022 Jan 14;375(6577):eabi4343. doi: 10.1126/science.abi4343. Epub 2022 Jan 14.


The outer mitochondrial membrane (OMM) is essential for cellular homeostasis. Yet little is known of the mechanisms that remodel it during natural stresses. We found that large “SPOTs” (structures positive for OMM) emerge during Toxoplasma gondii infection in mammalian cells. SPOTs mediated the depletion of the OMM proteins mitofusin 1 and 2, which restrict parasite growth. The formation of SPOTs depended on the parasite effector TgMAF1 and the host mitochondrial import receptor TOM70, which is required for optimal parasite proliferation. TOM70 enabled TgMAF1 to interact with the host OMM translocase SAM50. The ablation of SAM50 or the overexpression of an OMM-targeted protein promoted OMM remodeling independently of infection. Thus, Toxoplasma hijacks the formation of SPOTs, a cellular response to OMM stress, to promote its growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • GTP Phosphohydrolases / metabolism
  • Humans
  • Intracellular Membranes / physiology
  • Intracellular Membranes / ultrastructure
  • Mice
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Membranes / physiology*
  • Mitochondrial Membranes / ultrastructure
  • Mitochondrial Precursor Protein Import Complex Proteins / metabolism*
  • Mitochondrial Proteins / metabolism
  • Protein Binding
  • Protozoan Proteins / metabolism*
  • Stress, Physiological
  • Toxoplasma / growth & development
  • Toxoplasma / physiology*
  • Toxoplasma / ultrastructure
  • Toxoplasmosis / parasitology
  • Vacuoles / physiology
  • Vacuoles / ultrastructure


  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Mitochondrial Proteins
  • Protozoan Proteins
  • SAMM50 protein, human
  • TOMM70 protein, human
  • Tom70 protein, mouse
  • GTP Phosphohydrolases
  • MFN2 protein, human
  • Mfn1 protein, mouse
  • Mfn2 protein, mouse
  • Mfn1 protein, human