Search results for TOMM7

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Protein (3 results from a total of 3)

Identifier: R-HSA-1252079
Species: Homo sapiens
Compartment: mitochondrial outer membrane
Primary external reference: UniProt: TOMM7: Q9P0U1
Identifier: R-HSA-1252129
Species: Homo sapiens
Compartment: mitochondrial outer membrane
Primary external reference: UniProt: TOMM70: O94826
Identifier: R-HSA-6783033
Species: Homo sapiens
Compartment: mitochondrial outer membrane
Primary external reference: UniProt: TOMM70: O94826

Interactor (1 results from a total of 1)

Identifier: Q75MR5
Species: Homo sapiens
Primary external reference: UniProt: Q75MR5

Reaction (2 results from a total of 2)

Identifier: R-HSA-9709842
Species: Homo sapiens
Compartment: mitochondrial outer membrane
Mitochondrial import receptor subunit TOM70 (TOMM70) recognizes mitochondrial protein precursors in the cytosol and mediates their transition to the mitochondrial compartments (reviewed in Fan ACY & Young JC et al. 2011; Sokol AM et al. 2014; Kreimendahl S & Rassow J 2020). The molecular chaperone complexes of heat shock protein 90 kDa (HSP90) and HSP70 deliver precursor proteins to TOMM70 for subsequent import (Young JC et al. 2003; Zanphorlin LM et al. 2016).

During viral infection, cytosolic viral RNA triggers activation of mitochondrial antiviral-signaling protein (MAVS) and the formation of MAVS signalosome (Kawai T et al. 2005; Seth RB et al. 2005; Xu LG et al. 2005). MAVS localizes on the outer membrane of mitochondria through its C-terminal transmembrane (TM) domain. Activated MAVS recruits TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) to mitochondria leading to the activation of IRF3 and subsequent production of type I interferons.

Immunoprecipitation assays coupled to mass spectrometry analysis revealed that TOMM70 interacted with exogenously expressed MAVS in Sendai virus (SeV)-stimulated human embryonic kidney (HEK293) cells (Liu XY et al. 2010). The TM domains of both MAVS and TOMM70 were required for their interaction. In addition, TOMM70 interacted strongly with the C-terminal motif (EEVD) of HSP90 (Liu XY et al. 2010; Gava LM et al. 2011). TOMM70 also co-immunoprecipitated with TBK1 and IRF3 in HEK293 cells (Liu XY et al. 2010). Further, both TBK1 and IRF3 were found to associate with HSP90, which facilitated signal transduction from TBK1 to IRF3 in SeV-infected HEK293 cells (Yang K et l. 2006). Moreover, SeV infection enhanced the interaction between IRF3 and apoptosis regulator BAX (BAX) in HEK293T cells (Wei B et al. 2015). In SeV-stimulated HEK293 cells, cytosolic BAX translocated to the mitochondrial outer membrane and induced apoptosis in the IRF3-dependent manner via the formation of the TOMM70:HSP90:IRF3:BAX protein complex (Wei B et al. 2015). Knockdown of HSP90 by small interfering RNA (siRNA) decreased the association of TOMM70 with TBK1 and IRF3 (Liu XY et al. 2010). Overexpression of TOMM70 enhanced mRNA levels of IRF3-responsive genes (including IFNB, IFIT1 and RANTES) in HEK293 cells during SeV infection or poly(I:C) stimulation, whereas knockdown of TOMM70 by siRNA showed an inhibitory effect. Similar results were obtained in murine bone marrow-derived macrophages and bone marrow-derived dendritic cells (Liu XY et al. 2010). Thus, the association of MAVS with TOMM70 is thought to potentiate the HSP90-mediated recruitment of TBK1and IRF3 to mitochondria during viral infection thereby inducing IRF3-mediated host antiviral responses. In addition, binding of MAVS to TOMM70 can also trigger BAX-dependent apoptosis (Wei B et al. 2015). TOMM70 also associated with TRADD, TRAF6 and STING in HEK293 cells, further indicating that TOMM70 is a component of MAVS signal complex on mitochondria (Liu XY et al. 2010).

The viral orf9b (9b) proteins derived from SARS‑CoV-1 and SARS-CoV-2 inhibit the MAVS-mediated production of type I IFNs by targeting TOMM70 on the mitochondria (Jiang HW et al. 2020).

This Reactome event shows the association of MAVS with TOMM70.

Identifier: R-HSA-1268022
Species: Homo sapiens
Compartment: cytosol, mitochondrial outer membrane, mitochondrial intermembrane space
As inferred from the yeast TOM40:TOM70 complex, the human TOMM40:TOMM70 complex transports precursor proteins from the cytosol, across the outer membrane of the mitochondrion, and into the intermembrane space from where they may be targeted to all locations within the mitochondrion. As inferred from yeast, TOMM40, TOMM22, TOMM5, TOMM6, and TOMM7 probably form the general import pore across the membrane. On the cytosolic side TOMM20 and TOMM22 interact with presequences on mitochondrial precursors while TOMM70 interacts with hydrophobic sequences in mature internal regions of mitochondrial proteins.
In yeast, experimentally verified substrates of the TOM40:TOM70 complex include ATP1 (ATP5A1 in human), ATP2 (ATP5B in human), ATP9 (ATP5G1 in human), TOM40 (TOMM40 in human), SSC1 (mtHsp70, HSPA9 in human), CIT1 (CS in human), ACO1 (ACO2 in human), IDH1 (IDH3G in human), BCS1 (BCS1L in human), CYT1 (CYC1 in human), TIM54 (TIMM54 in human), TIM22 (TIMM22 in human), AAC (ADP/ATP translocase 1, ANT, SLC25A4 in human), HSP60, and CYB2. In humans, TOMM40 has been shown to be a substrate (Humphries et al. 2005). In yeast some proteins such as ACO1, ATP1, CIT1, IDH1, and ATP2 contain both presequences that interact with TOM20 and mature regions that interact with TOM70 (Yamamoto et al. 2009). Most proteins imported into mitochondria are anticipated to be transported through the TOMM40:TOMM70 complex.

Complex (1 results from a total of 1)

Identifier: R-HSA-1252240
Species: Homo sapiens
Compartment: mitochondrial outer membrane
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