研究人员发现哺乳动物细胞在弓形虫感染期间出现了大型“SPOTs”（structures positive for OMM）结构。SPOTs介导了OMM蛋白MFN1(mitofusin 1)和MFN2(mitofusin 2)的消耗，从而限制了寄生虫的生长。SPOTs的形成依赖于寄生虫效应因子TgMAF1和宿主线粒体输入受体TOM70。TOM70使TgMAF1能够与宿主OMM 易位酶SAM50相互作用。
在没有病原体感染的情况下，SAM50的缺失或OMM靶向蛋白的过表达也能够促进OMM结构重塑。因此，弓形虫感染促进了 SPOTs 的形成，这是一种对 OMM 应激的细胞反应，以保护线粒体功能促进细胞的生长。
据悉，外线粒体膜(outer mitochondrial membrane, OMM)对细胞内环境的稳态至关重要。然而，人们对OMM在自然压力下的重塑机制知之甚少。
附：英文原文
Title: Mitochondria shed their outer membrane in response to infection-induced stress
Author: Xianhe Li, Julian Straub, Tania 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
Issue&Volume: 2022-01-14
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.
DOI: abi4343
Source: https://www.science.org/doi/10.1126/science.abi4343