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

Xianhe Li; Julian Straub; Tânia Catarina Medeiros; Chahat Mehra; Fabian den Brave; Esra Peker; Ilian Atanassov; Katharina Stillger; Jonas Benjamin Michaelis; Emma Burbridge; Colin Adrain; Christian Münch; Jan Riemer; Thomas Becker; Lena F Pernas

doi:10.1126/science.abi4343

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

Xianhe Li, Julian Straub, Tânia Catarina Medeiros, Chahat Mehra, Fabian den Brave, Esra Peker, Ilian Atanassov, Katharina Stillger, Jonas Benjamin Michaelis, Emma Burbridge, Colin Adrain, Christian Münch, Jan Riemer, Thomas Becker, Lena F Pernas

Patrick G Johnston Centre for Cancer Research

Research output: Contribution to journal › Article › peer-review

52 Citations (Scopus)

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.

Original language	English
Article number	eabi4343
Journal	Science
Volume	375
Issue number	6577
DOIs	https://doi.org/10.1126/science.abi4343
Publication status	Published - 14 Jan 2022

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title = "Mitochondria shed their outer membrane in response to infection-induced stress",

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.",

author = "Xianhe Li and Julian Straub and Medeiros, {T{\^a}nia Catarina} and Chahat Mehra and {den Brave}, Fabian and Esra Peker and Ilian Atanassov and Katharina Stillger and Michaelis, {Jonas Benjamin} and Emma Burbridge and Colin Adrain and Christian M{\"u}nch and Jan Riemer and Thomas Becker and Pernas, {Lena F}",

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doi = "10.1126/science.abi4343",

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T1 - Mitochondria shed their outer membrane in response to infection-induced stress

AU - Li, Xianhe

AU - Straub, Julian

AU - Medeiros, Tânia Catarina

AU - Mehra, Chahat

AU - den Brave, Fabian

AU - Peker, Esra

AU - Atanassov, Ilian

AU - Stillger, Katharina

AU - Michaelis, Jonas Benjamin

AU - Burbridge, Emma

AU - Adrain, Colin

AU - Münch, Christian

AU - Riemer, Jan

AU - Becker, Thomas

AU - Pernas, Lena F

PY - 2022/1/14

Y1 - 2022/1/14

N2 - 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.

AB - 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.

U2 - 10.1126/science.abi4343

DO - 10.1126/science.abi4343

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SN - 0036-8075

VL - 375

JO - Science

JF - Science

IS - 6577

M1 - eabi4343

ER -

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

Abstract

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