Regulation of astrocyte metabolism by mitochondrial translocator protein 18 kDa
dc.contributor.author | Firth, W | |
dc.contributor.author | Robb, JL | |
dc.contributor.author | Stewart, D | |
dc.contributor.author | Pye, KR | |
dc.contributor.author | Bamford, R | |
dc.contributor.author | Oguro-Ando, A | |
dc.contributor.author | Beall, C | |
dc.contributor.author | Ellacott, KLJ | |
dc.date.accessioned | 2024-03-21T13:33:54Z | |
dc.date.issued | 2024-03-14 | |
dc.date.updated | 2024-03-21T11:47:29Z | |
dc.description.abstract | The mitochondrial translocator protein 18 kDa (TSPO) has been linked to functions from steroidogenesis to regulation of cellular metabolism and is an attractive therapeutic target for chronic CNS inflammation. Studies in Leydig cells and microglia indicate that TSPO function may vary between cells depending on their specialized roles. Astrocytes are critical for providing trophic and metabolic support in the brain. Recent work has highlighted that TSPO expression increases in astrocytes under inflamed conditions and may drive astrocyte reactivity. Relatively little is known about the role TSPO plays in regulating astrocyte metabolism and whether this protein is involved in immunometabolic processes in these cells. Using TSPO-deficient (TSPO-/- ) mouse primary astrocytes in vitro (MPAs) and a human astrocytoma cell line (U373 cells), we performed extracellular metabolic flux analyses. We found that TSPO deficiency reduced basal cellular respiration and attenuated the bioenergetic response to glucopenia. Fatty acid oxidation was increased, and lactate production was reduced in TSPO-/- MPAs and U373 cells. Co-immunoprecipitation studies revealed that TSPO forms a complex with carnitine palmitoyltransferase 1a in U373 and MPAs, presenting a mechanism wherein TSPO may regulate FAO in these cells. Compared to TSPO+/+ cells, in TSPO-/- MPAs we observed attenuated tumor necrosis factor release following 3 h lipopolysaccharide (LPS) stimulation, which was enhanced at 24 h post-LPS stimulation. Together these data suggest that while TSPO acts as a regulator of metabolic flexibility, TSPO deficiency does not appear to modulate the metabolic response of MPAs to inflammation, at least in response to the model used in this study. | en_GB |
dc.description.sponsorship | British Society for Neuroendocrinology | en_GB |
dc.description.sponsorship | Research England | en_GB |
dc.description.sponsorship | University of Exeter | en_GB |
dc.format.medium | Print-Electronic | |
dc.identifier.citation | Published online 14 March 2024 | en_GB |
dc.identifier.doi | https://doi.org/10.1111/jnc.16089 | |
dc.identifier.uri | http://hdl.handle.net/10871/135600 | |
dc.identifier | ORCID: 0000-0003-4029-3250 (Oguro-Ando, Asami) | |
dc.identifier | ORCID: 0000-0002-4263-0866 (Beall, Craig) | |
dc.identifier | ScopusID: 36175475800 (Beall, Craig) | |
dc.identifier | ORCID: 0000-0001-5261-7465 (Ellacott, Kate LJ) | |
dc.language.iso | en | en_GB |
dc.publisher | Wiley / International Society for Neurochemistry | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/38482552 | en_GB |
dc.rights | © 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | en_GB |
dc.subject | TSPO | en_GB |
dc.subject | astrocyte | en_GB |
dc.subject | cytokine release | en_GB |
dc.subject | fatty acid oxidation | en_GB |
dc.subject | inflammation | en_GB |
dc.subject | metabolism | en_GB |
dc.title | Regulation of astrocyte metabolism by mitochondrial translocator protein 18 kDa | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2024-03-21T13:33:54Z | |
dc.identifier.issn | 0022-3042 | |
exeter.place-of-publication | England | |
dc.description | This is the final version. Available on open access from Wiley via the DOI in this record | en_GB |
dc.description | Data availability statement: The datasets used and analyzed during this study are available from the corresponding author upon receipt of reasonable request. | en_GB |
dc.identifier.eissn | 1471-4159 | |
dc.identifier.journal | Journal of Neurochemistry | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2024-02-17 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2024-03-14 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2024-03-21T13:30:30Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2024-03-21T13:34:03Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2024-03-14 |
Files in this item
This item appears in the following Collection(s)
Except where otherwise noted, this item's licence is described as © 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.