2. Academic Validation
  3. Mitochondria shed their outer membrane in response to infection-induced stress

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

  • Science. 2022 Jan 14;375(6577):eabi4343. doi: 10.1126/science.abi4343.
Xianhe Li 1,  Julian Straub 1,  Tânia Catarina Medeiros 1,  Chahat Mehra 1,  Fabian den Brave 2,  Esra Peker 3,  Ilian Atanassov 1,  Katharina Stillger 3,  Jonas Benjamin Michaelis 4,  Emma Burbridge 5 6,  Colin Adrain 5 6,  Christian Münch 4,  Jan Riemer 3 7,  Thomas Becker 2,  Lena F Pernas 1 7
Affiliations

Affiliations

  • 1 Max Planck Institute for Biology of Ageing, Cologne, Germany.
  • 2 Institute of Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, Bonn, Germany.
  • 3 Institute of Biochemistry, University of Cologne, Cologne, Germany.
  • 4 Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany.
  • 5 Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland.
  • 6 Instituto Gulbenkian de Ciência, Oeiras, Portugal.
  • 7 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
PMID: 35025629 DOI: 10.1126/science.abi4343
Abstract

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.

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