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- Kohler, Andreas, Dr. rer. nat. 1988-, et al.
(author)
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Early fate decision for mitochondrially encoded proteins by a molecular triage
- 2023
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In: Molecular Cell. - : Cell Press. - 1097-2765 .- 1097-4164. ; 83:19
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Journal article (peer-reviewed)abstract
- Folding of newly synthesized proteins poses challenges for a functional proteome. Dedicated protein quality control (PQC) systems either promote the folding of nascent polypeptides at ribosomes or, if this fails, ensure their degradation. Although well studied for cytosolic protein biogenesis, it is not understood how these processes work for mitochondrially encoded proteins, key subunits of the oxidative phosphorylation (OXPHOS) system. Here, we identify dedicated hubs in proximity to mitoribosomal tunnel exits coordinating mitochondrial protein biogenesis and quality control. Conserved prohibitin (PHB)/m-AAA protease supercomplexes and the availability of assembly chaperones determine the fate of newly synthesized proteins by molecular triaging. The localization of these competing activities in the vicinity of the mitoribosomal tunnel exit allows for a prompt decision on whether newly synthesized proteins are fed into OXPHOS assembly or are degraded.
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| 2. |
- Olofsson Bagge, Roger, 1978, et al.
(author)
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Three-dimensional reconstruction of interstitial extracellular vesicles in human liver as determined by electron tomography
- 2023
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In: Journal of Extracellular Vesicles. - 2001-3078. ; 12:12
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Journal article (peer-reviewed)abstract
- Extracellular vesicles (EVs) are lipid bilayer nanoparticles involved in cell-cell communication that are released into the extracellular space by all cell types. The cargo of EVs includes proteins, lipids, nucleic acids, and metabolites reflecting their cell of origin. EVs have recently been isolated directly from solid tissues, and this may provide insights into how EVs mediate communication between cells in vivo. Even though EVs have been isolated from tissues, their point of origin when they are in the interstitial space has been uncertain. In this study, we performed three-dimensional (3D) reconstruction using transmission electron tomography of metastatic and normal liver tissues with a focus on the presence of EVs in the interstitium. After chemical fixation of the samples and subsequent embedding of tissue pieces in resin, ultrathin slices (300 nm) were cut and imaged on a 120 ekV transmission electron microscopy as a tilt series (a series of subsequent images tilted at different angles). These were then computationally illustrated in a 3D manner to reconstruct the imaged tissue volume. We identified the cells delimiting the interstitial space in both types of tissues, and small distinct spherical structures with a diameter of 30-200 nm were identified between the cells. These round structures appeared to be more abundant in metastatic tissue compared to normal tissue. We suggest that the observed spherical structures in the interstitium of the metastatic and non-metastatic liver represent EVs. This work thus provides the first 3D visualization of EVs in human tissue. Three-dimensional (3D) reconstruction of both liver metastases and normal liver, using transmission electron tomography, identified spherical structures with a diameter of 30-200 nm in the interstitium of both types of tissues.image
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