The receptor subunit Tom20 is dynamically associated with the TOM complex in mitochondria of human cells

Bhagawati, Maniraj; Arroum, Tasnim; Webeling, Niklas; Montoro, Ayelén González; Mootz, Henning D.; Busch, Karin B.

doi:10.1091/mbc.e21-01-0042

Cited by 25 publications

(13 citation statements)

References 38 publications

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“…In addition, we show the interaction of VLGR1 with TOM20, a peripheral subunit of the mitochondrial outer membrane translocase essential of mitochondrial protein import. It has been recently shown that TOM20 forms a complex with the VDAC1 and cooperates in channeling Ca 2+ ions into mitochondria [ 68 ]. It is worth noting that both voltage-dependent anion channels VDAC1 and VDAC2 were also found to be hits in the VLGR1 TAPs (see Table 1 ), so they also represent potential binding partners of VLGR1 in a protein complex related to VLGR1 in the MAM compartment (see cartoon, Figure 2 E).…”

Section: Discussionmentioning

confidence: 99%

The Adhesion GPCR VLGR1/ADGRV1 Regulates the Ca2+ Homeostasis at Mitochondria-Associated ER Membranes

Krzysko

Maciąg

Mertens

et al. 2022

Cells

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The very large G protein-coupled receptor (VLGR1, ADGRV1) is the largest member of the adhesion GPCR family. Mutations in VLGR1 have been associated with the human Usher syndrome (USH), the most common form of inherited deaf-blindness as well as childhood absence epilepsy. VLGR1 was previously found as membrane–membrane adhesion complexes and focal adhesions. Affinity proteomics revealed that in the interactome of VLGR1, molecules are enriched that are associated with both the ER and mitochondria, as well as mitochondria-associated ER membranes (MAMs), a compartment at the contact sites of both organelles. We confirmed the interaction of VLGR1 with key proteins of MAMs by pull-down assays in vitro complemented by in situ proximity ligation assays in cells. Immunocytochemistry by light and electron microscopy demonstrated the localization of VLGR1 in MAMs. The absence of VLGR1 in tissues and cells derived from VLGR1-deficient mouse models resulted in alterations in the MAM architecture and in the dysregulation of the Ca2+ transient from ER to mitochondria. Our data demonstrate the molecular and functional interaction of VLGR1 with components in MAMs and point to an essential role of VLGR1 in the regulation of Ca2+ homeostasis, one of the key functions of MAMs.

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Section: Discussionmentioning

confidence: 99%

The Adhesion GPCR VLGR1/ADGRV1 Regulates the Ca2+ Homeostasis at Mitochondria-Associated ER Membranes

Krzysko

Maciąg

Mertens

et al. 2022

Cells

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“…Phalloidin, Concanavalin A, and WGA, while highlighting organelles and cellular components, also work as cell segmentation markers, and are therefore less specific 29 . While TOM20 and HSP60 both colocalize in mitochondria, HSP60 can also be found in extramitochondrial regions such as the cytosol, vesicles, and the cell membrane 30 – 32 . Similarly, Sortilin can be found in regions other than the Golgi, such as endosomes and lysosomes, whereas GOLPH4 is predominantly localized in the Golgi 33 , 34 .…”

Section: Resultsmentioning

confidence: 99%

Spatial subcellular organelle networks in single cells

Venkatesan

Zhang

Marteau

et al. 2023

Sci Rep

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Organelles play important roles in human health and disease, such as maintaining homeostasis, regulating growth and aging, and generating energy. Organelle diversity in cells not only exists between cell types but also between individual cells. Therefore, studying the distribution of organelles at the single-cell level is important to understand cellular function. Mesenchymal stem cells are multipotent cells that have been explored as a therapeutic method for treating a variety of diseases. Studying how organelles are structured in these cells can answer questions about their characteristics and potential. Herein, rapid multiplexed immunofluorescence (RapMIF) was performed to understand the spatial organization of 10 organelle proteins and the interactions between them in the bone marrow (BM) and umbilical cord (UC) mesenchymal stem cells (MSCs). Spatial correlations, colocalization, clustering, statistical tests, texture, and morphological analyses were conducted at the single cell level, shedding light onto the interrelations between the organelles and comparisons of the two MSC subtypes. Such analytics toolsets indicated that UC MSCs exhibited higher organelle expression and spatially spread distribution of mitochondria accompanied by several other organelles compared to BM MSCs. This data-driven single-cell approach provided by rapid subcellular proteomic imaging enables personalized stem cell therapeutics.

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“…Following this line of interpretation, we investigated mitochondria (Fig. 4), as they contribute most of the cells NADH production, by quantifying mitochondrial import receptor subunit TOM20 located on the outer mitochondrial membrane (Bhagawati et al 2021) and clustered mitochondria protein homolog (CLUH). The latter has been connected to mitochondrial fission, the splitting of one mitochondria in two daughter mitochondria, a process tightly connected to quality control of mitochondria (Westermann 2010;Yang et al 2022).…”

Section: Discussionmentioning

confidence: 99%

Activation of autophagy triggers mitochondrial loss and changes acetylation profile relevant for mechanotransduction in bladder cancer cells

et al. 2022

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Bladder cells are constantly exposed to multiple xenobiotics and bioactive metabolites. In addition to this challenging chemical environment, they are also exposed to shear stress originating from urine and interstitial fluids. Hence, physiological function of bladder cells relies on a high biochemical and biomechanical adaptive competence, which, in turn, is largely supported via autophagy-related mechanisms. As a negative side of this plasticity, bladder cancer cells are known to adapt readily to chemotherapeutic programs. At the molecular level, autophagy was described to support resistance against pharmacological treatments and to contribute to the maintenance of cell structure and metabolic competence. In this study, we enhanced autophagy with rapamycin (1–100 nM) and assessed its effects on the motility of bladder cells, as well as the capability to respond to shear stress. We observed that rapamycin reduced cell migration and the mechanical-induced translocation potential of Krüppel-like transcription factor 2 (KLF2). These effects were accompanied by a rearrangement of cytoskeletal elements and mitochondrial loss. In parallel, intracellular acetylation levels were decreased. Mechanistically, inhibition of the NAD + -dependent deacetylase sirtuin-1 (SIRT1) with nicotinamide (NAM; 0.1–5 mM) restored acetylation levels hampered by rapamycin and cell motility. Taken together, we described the effects of rapamycin on cytoskeletal elements crucial for mechanotransduction and the dependency of these changes on the mitochondrial turnover caused by autophagy activation. Additionally, we could show that targeted metabolic intervention could revert the outcome of autophagy activation, reinforcing the idea that bladder cells can easily adapt to multiple xenobiotics and circumvent in this way the effects of single chemicals.

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The receptor subunit Tom20 is dynamically associated with the TOM complex in mitochondria of human cells

Cited by 25 publications

References 38 publications

The Adhesion GPCR VLGR1/ADGRV1 Regulates the Ca2+ Homeostasis at Mitochondria-Associated ER Membranes

The Adhesion GPCR VLGR1/ADGRV1 Regulates the Ca2+ Homeostasis at Mitochondria-Associated ER Membranes

Spatial subcellular organelle networks in single cells

Activation of autophagy triggers mitochondrial loss and changes acetylation profile relevant for mechanotransduction in bladder cancer cells

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