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

Xianhe Li1, Julian Straub1, Tânia Catarina Medeiros1

  • 1Max Planck Institute for Biology of Ageing, Cologne, Germany.

Science (New York, N.Y.)
|January 13, 2022
PubMed

Insights

Toxoplasma gondii infection triggers the formation of large structures called SPOTs on the outer mitochondrial membrane (OMM). This process depletes OMM proteins, promoting parasite growth.

Area of Science:

  • Cell Biology
  • Parasitology
  • Mitochondrial Biology

Background:

  • The outer mitochondrial membrane (OMM) is crucial for cellular function.
  • Mechanisms of OMM remodeling during cellular stress are not well understood.
  • Toxoplasma gondii infection impacts host cell homeostasis.

Purpose of the Study:

  • To investigate the remodeling of the OMM during Toxoplasma gondii infection.
  • To identify host and parasite factors involved in OMM changes.
  • To understand how these OMM changes affect parasite proliferation.

Main Methods:

  • Observation of "SPOTs" (structures positive for OMM) in infected mammalian cells.
  • Analysis of OMM protein depletion (mitofusin 1 and 2).
  • Investigating the roles of parasite effector TgMAF1 and host receptor TOM70.

Main Results:

  • Large SPOTs form on the OMM during T. gondii infection.
  • SPOTs lead to the depletion of mitofusin 1 and 2, hindering parasite growth restriction.
  • Parasite effector TgMAF1 and host receptor TOM70 are essential for SPOT formation.
  • TOM70 facilitates TgMAF1 interaction with SAM50, an OMM translocase.

Conclusions:

  • Toxoplasma gondii hijacks the host's OMM stress response pathway (SPOT formation) to promote its own growth.
  • The parasite manipulates OMM protein levels via TgMAF1, TOM70, and SAM50.
  • OMM remodeling can be induced independently of infection, highlighting its role in cellular stress responses.

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