Dataset Information

Mitochondria shed large SPOTs during infection-induced import stress to remodel their outer membrane

ABSTRACT: Despite the essential role of the outer mitochondrial membrane (OMM) in cellular homeostasis, little is known of the mechanisms that remodel it during naturally occurring stresses. Here, we report a previously undescribed structure we term SPOT (structure positive for outer mitochondrial membrane) that is up to 10 m in diameter and emerges from the OMM during infection with the human parasite Toxoplasma gondii. SPOTs are distinct from mitochondria-derived vesicles and compartments, and mediate the depletion of the OMM proteins MFN1 and MFN2 that restrict parasite growth. The formation of SPOTs depends on the parasite effector protein TgMAF1 and the host mitochondrial import receptor TOM70, which is required for optimal parasite proliferation. TOM70 enables TgMAF1 to interact with host SAM50, a major translocase of the OMM, and SAM50 inhibition or acute mitochondrial import stress are sufficient to promote SPOT formation independently of infection. We propose that Toxoplasma exploits SPOTs, a cellular response to OMM import stress, to promote its growth.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive HF

ORGANISM(S): Homo Sapiens (human) Toxoplasma Gondii

SUBMITTER: Ilian Atanassov

LAB HEAD: Lena Pernas

PROVIDER: PXD024491 | Pride | 2022-08-04

REPOSITORIES: Pride

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	190322_QE_Li_Lena_Cell_19_75cm_220min_4ug.raw	Raw
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Mitochondria shed their outer membrane in response to infection-induced stress.

Li Xianhe X Straub Julian J Medeiros Tânia Catarina TC Mehra Chahat C den Brave Fabian F Peker Esra E Atanassov Ilian I Stillger Katharina K Michaelis Jonas Benjamin JB Burbridge Emma E Adrain Colin C Münch Christian C Riemer Jan J Becker Thomas T Pernas Lena F LF

Science (New York, N.Y.) 20220114 6577

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 <i>Toxoplasma gondii</i> 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, wh ...[more]

PMID: 35025629

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