TOMM70

更新于：2025-05-07

基本信息

别名

KIAA0719、Mitochondrial import receptor subunit TOM70、Mitochondrial precursor proteins import receptor

+ [6]

简介

Acts as a receptor of the preprotein translocase complex of the outer mitochondrial membrane (TOM complex) (PubMed:12526792). Recognizes and mediates the translocation of mitochondrial preproteins from the cytosol into the mitochondria in a chaperone dependent manner (PubMed:12526792, PubMed:35025629). Mediates TBK1 and IRF3 activation induced by MAVS in response to Sendai virus infection and promotes host antiviral responses during virus infection (PubMed:20628368, PubMed:25609812, PubMed:32728199). Upon Sendai virus infection, recruits HSP90AA1:IRF3:BAX in mitochondrion and the complex induces apoptosis (PubMed:25609812).

关联

100 项与 TOMM70 相关的临床结果

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100 项与 TOMM70 相关的转化医学

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0 项与 TOMM70 相关的专利（医药）

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256

项与 TOMM70 相关的文献（医药）

2025-05-01·Journal of Trauma and Acute Care Surgery

Cell-free mitochondria are detected in high concentrations in the plasma of orthopedic trauma patients

Article

作者: Meakes, Simone ; Balogh, Zsolt J ; Briggs, Gabrielle D ; King, Kate L

BACKGROUNDTrauma and surgery can derange inflammatory and hemostasis responses, potentially leading to multiple organ failure. Mitochondrial damage-associated molecular patterns are known to be part of the pathomechanism, but their exact origin remains uncertain. Recently, intact mitochondria were detected in healthy individuals' peripheral blood, which suggested a potential role in inflammation.METHODSIn this case-control study, we quantitated cell-free mitochondria in the blood of healthy subjects (n = 4) and trauma patients (n = 25) and assessed their relationship with patient demographics, injury and shock severity, markers of tissue injury, inflammation, and blood transfusions. Blood samples were collected before and after major orthopedic trauma surgery, and cell-free mitochondria were quantified using flow cytometry, targeting the outer mitochondrial membrane protein, TOMM70. Mitotracker Deep Red staining was used to assess mitochondrial membrane potential.RESULTSTrauma patients had significantly more cell-free mitochondria in their plasma compared with healthy controls, with highest counts immediately after surgery. The number of cell-free mitochondria decreased by day 5 postoperatively. Trauma patients exhibited a higher proportion of active cell-free mitochondria compared with healthy controls, especially immediately after surgery, and this proportion correlated with tissue injury markers. Associations were also found with acute thrombocytopenia, Denver multiple organ failure score, and transfusion of fresh frozen plasma and cryoprecipitate.CONCLUSIONOur findings indicate that the mere high number of cell-free mitochondria in the circulation of trauma patients is not necessarily pro-inflammatory, but their active status is associated with more severe secondary tissue injury. The natural history of cell-free mitochondria in trauma needs to be characterized, including their potential cause-effect relationship with major postinjury complications.LEVEL OF EVIDENCEPrognostic and Epidemiological; Level III.

2025-05-01·Veterinary Microbiology

The depletion of TFAM and p-β-catenin(S552) in mitochondria in response to BoAHV-1 productive infection leads to decreased mitochondrial biogenesis

Article

作者: Lin, Jiayu ; Ding, Xiuyan ; Fiorito, Filomena ; Fu, Xiaotian ; Li, Xuan ; Li, Shitao ; Zhu, Liqian

Varicellovirus bovinealpha (BoAHV) types 1(BoAHV-1) is one of the most significant viruses affecting cattle, causing substantial economic losses in the global cattle industry. Virus productive infection in cell cultures leads to mitochondrial dysfunction, resulting in the overproduction of reactive oxygen species (ROS), which act as inflammatory mediators and exert cytotoxic effects. But the underlying mechanisms remain poorly understood. Mitochondrial transcription factor A (TFAM) is a critical transcriptional activator of the mitochondrial DNA and plays a vital role in mitochondrial biogenesis. In this study, we report that virus acute infection in calves (at 4 days post-infection) increases TFAM protein expression and its accumulation in the peri-nuclear region in a subset of trigeminal ganglia (TG) neurons. Similarly, virus productive infection at later stages in MDBK cells also leads to increased TFAM protein expression and its accumulation in the nucleus. Using TFAM-specific siRNAs, we revealed that TFAM plays a significant role in BoAHV-1 productive infection. Consistent with decreased mitochondrial biogenesis, TFAM protein accumulation in mitochondria was significantly reduced following viral infection, which is corroborated by the reduced accumulation of TOM70 and Tim44 proteins in mitochondria. These proteins are key components of the mitochondrial membrane transport system that facilitates the translocation of TFAM into mitochondria. Interestingly, we found that a subset of β-catenin resides in mitochondria, and viral infection decreases the accumulation of transcriptionally active β-catenin, p-β-catenin(S552), in mitochondria. This may contribute to decreased mitochondrial biogenesis, as the β-catenin-specific inhibitor iCRT14 reduces the protein expression of Cytb, a key regulator of mitochondrial biosynthesis. Collectively, we suggest that the depletion of both TFAM and p-β-catenin(S552) in mitochondria may contribute to the mitochondrial dysfunction induced by BoAHV-1 productive infection.

2025-04-01·Atherosclerosis

Simvastatin ameliorates senescence-induced mitochondrial dysfunction in vascular smooth muscle cells

Article

作者: Battaglia, C ; Rossi, C ; Ruscica, M ; Venturin, M ; Corsini, A ; D'Alonzo, C ; Bellosta, S ; Macchi, C

BACKGROUND AND AIMSSenescence and mitochondrial dysfunction are two major indicators of aging. Mitochondria are potential drivers of aging phenotypes and dysfunctional mitochondria are associated with several age-related diseases. There is evidence that senescence induces changes in mitochondrial structure, dynamics, and function. Moreover, senescent vascular smooth muscle cells (VSMCs) are present in atherosclerotic plaques and contribute to their instability. The anti-atherosclerotic effects of simvastatin are well known, but recently other benefits, such as promoting mitochondrial quality and senostatic effects, have been hypothesized. We aimed to analyze simvastatin's senostatic effects in senescent VSMCs.METHODSWe established and characterized mitochondrial dysfunction in doxorubicin-induced senescent VSMCs (doxorubicin) or VSMCs serially passaged to induce replicative senescence (old).RESULTSWe observed in both senescent models few typical senescence markers such as altered cell morphology, cell cycle inhibitors, laminB1, an accumulation of dysfunctional mitochondria characterized by reduced mitochondrial membrane potential (MMP) and respiration, accumulation of reactive oxygen species (ROS), and an altered mitochondria morphology. Down-regulation of TFAM and TOM70 expression was observed only in old cells suggesting a reduction of mitochondrial biogenesis. Next, we investigated whether simvastatin could ameliorate age-associated phenotypes in senescent VSMCs. Simvastatin 0.1 μM reduces the senescence-associated secretory phenotype (SASP) and ROS production and improves mitochondrial respiration in doxorubicin and old VSMCs. Interestingly, the effects of simvastatin on mitochondrial respiration and SASP were replicated by using a siRNA for the hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, and abolished by adding mevalonic acid, suggesting that these effects are mediated through the inhibition of HMG-CoA reductase.CONCLUSIONSOur results suggest that simvastatin controls SASP and exerts potentially beneficial therapeutic effects by ameliorating senescence-induced mitochondrial dysfunction in senescent VSMCs.

项与 TOMM70 相关的新闻（医药）

2022-06-27

·生物谷

Proc Natl Acad Sci U S A:报道Tom20和Tom22的胞质结构域作为线粒体TOM复合体受体的结构基础

隋森芳团队首先获得了人源线粒体TOM核心复合体（仅包含Tom40、Tom22、Tom5、Tom6、Tom7）的结构，分辨率高达2.53 Å，是目前该复合体的最高分辨率。线粒体作为真核细胞的重要细胞器在各种细胞活动中发挥不可忽视的作用，例如能量调节、细胞凋亡、自噬等。线粒体内有1500-2000种不同的蛋白协同完成各项功能，其中90%以上的蛋白都是在细胞质中合成的。因此，它们必须转运至线粒体内部才能发挥功能，这主要是通过TOM复合物完成的。定位于线粒体外膜的TOM复合物通过识别、传递、转运三个主要步骤将在细胞质中合成的蛋白转运至线粒体内部。在人体中，TOM复合物的缺陷和多种疾病相关，尤其是与帕金森综合症关系密切。完整的TOM复合物由7种不同的亚基构成，分别为β-桶结构用来形成通道的Tom40亚基；α-螺旋结构的受体蛋白Tom20、Tom22和Tom70；以及三个围绕Tom40的小亚基Tom5、Tom6和Tom7。虽然已有TOM复合物的结构发表，但由于受体亚基的不稳定性，发表的结构中都不包含Tom20、Tom70以及完整的Tom22胞质区，这极大限制了人们对于TOM复合物的转运机制的理解。清华大学生命科学学院隋森芳教授课题组在《美国科学院院报》（Proc Natl Acad Sci U S A）杂志上发表了题为：“Tom20和Tom22的胞质结构域作为人源线粒体TOM复合体受体的结构基础（Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors）”的研究论文。通过冷冻电镜单颗粒分析技术解析了包含Tom22及Tom20胞质区的TOM复合物的高分辨率结构，并进一步结合生物化学方法推测了TOM复合物转运蛋白的机制。隋森芳团队首先获得了人源线粒体TOM核心复合体（仅包含Tom40、Tom22、Tom5、Tom6、Tom7）的结构，分辨率高达2.53 Å，是目前该复合体的最高分辨率。该结构揭示了大量蛋白与蛋白以及磷脂与蛋白间的相互作用，这些相互作用对于维持TOM复合体的稳定性至关重要。他们进一步通过交联实验稳定TOM复合体，从而成功获得了包含受体蛋白Tom20及Tom22的胞质区的TOM复合体的结构，分辨率为3.74 Å。结构分析表明，Tom22的N端胞质结构域与Tom20的C端胞质结构域具有相似的三螺旋束结构。已有的研究表明Tom20的胞质结构域是被转运蛋白前序列（presequence）的主要结合位点，因此他们推测Tom22也可能通过其胞质结构域与前序列结合。进一步的生化实验结果证实了他们的猜想，并发现三螺旋束中的第一个螺旋对这种结合是关键的。这些结果为TOM复合体识别和跨线粒体膜转移蛋白的作用机制提供了深入的见解。生命学院隋森芳教授和孙珊副研究员为本文共同通讯作者。生命学院2018级博士生苏家跃、已出站博士后刘德生为本文的共同第一作者。清华大学冷冻电镜平台工程师杨帆参与了电镜数据分析；生命学院2019级博士生李畅参与了生化样品的制备；北京生命科学研究所董梦秋研究员和博士生左美晴进行了交联质谱的工作。国家蛋白质科学研究（北京）设施清华基地冷冻电镜平台和计算平台为数据收集和处理提供了支持。膜生物学国家重点实验室、北京市结构生物学高精尖创新中心、北京生物结构前沿研究中心、科技部、国家自然科学基金等为本研究提供了经费支持。人源TOM复合物的结构。 A，TOM核心复合物的结构。B，包含Tom22及Tom20胞质区的TOM复合物的结构论文链接：https://www.pnas.org/doi/10.1073/pnas.2200158119

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