Cargando…

Genetic analysis of dTSPO, an outer mitochondrial membrane protein, reveals its functions in apoptosis, longevity, and Aβ42-induced neurodegeneration

The outer mitochondrial membrane (OMM) protein, the translocator protein 18 kDa (TSPO), formerly named the peripheral benzodiazepine receptor (PBR), has been proposed to participate in the pathogenesis of neurodegenerative diseases. To clarify the TSPO function, we identified the Drosophila homolog,...

Descripción completa

Detalles Bibliográficos
Autores principales: Lin, Ran, Angelin, Alessia, Da Settimo, Federico, Martini, Claudia, Taliani, Sabrina, Zhu, Shigong, Wallace, Douglas C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076708/
https://www.ncbi.nlm.nih.gov/pubmed/24977274
http://dx.doi.org/10.1111/acel.12200
_version_ 1782323521921220608
author Lin, Ran
Angelin, Alessia
Da Settimo, Federico
Martini, Claudia
Taliani, Sabrina
Zhu, Shigong
Wallace, Douglas C
author_facet Lin, Ran
Angelin, Alessia
Da Settimo, Federico
Martini, Claudia
Taliani, Sabrina
Zhu, Shigong
Wallace, Douglas C
author_sort Lin, Ran
collection PubMed
description The outer mitochondrial membrane (OMM) protein, the translocator protein 18 kDa (TSPO), formerly named the peripheral benzodiazepine receptor (PBR), has been proposed to participate in the pathogenesis of neurodegenerative diseases. To clarify the TSPO function, we identified the Drosophila homolog, CG2789/dTSPO, and studied the effects of its inactivation by P-element insertion, RNAi knockdown, and inhibition by ligands (PK11195, Ro5-4864). Inhibition of dTSPO inhibited wing disk apoptosis in response to γ-irradiation or H(2)O(2) exposure, as well as extended male fly lifespan and inhibited Aβ42-induced neurodegeneration in association with decreased caspase activation. Therefore, dTSPO is an essential mediator of apoptosis in Drosophila and plays a central role in controlling longevity and neurodegenerative disease, making it a promising drug target.
format Online
Article
Text
id pubmed-4076708
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher BlackWell Publishing Ltd
record_format MEDLINE/PubMed
spelling pubmed-40767082015-02-19 Genetic analysis of dTSPO, an outer mitochondrial membrane protein, reveals its functions in apoptosis, longevity, and Aβ42-induced neurodegeneration Lin, Ran Angelin, Alessia Da Settimo, Federico Martini, Claudia Taliani, Sabrina Zhu, Shigong Wallace, Douglas C Aging Cell Original Articles The outer mitochondrial membrane (OMM) protein, the translocator protein 18 kDa (TSPO), formerly named the peripheral benzodiazepine receptor (PBR), has been proposed to participate in the pathogenesis of neurodegenerative diseases. To clarify the TSPO function, we identified the Drosophila homolog, CG2789/dTSPO, and studied the effects of its inactivation by P-element insertion, RNAi knockdown, and inhibition by ligands (PK11195, Ro5-4864). Inhibition of dTSPO inhibited wing disk apoptosis in response to γ-irradiation or H(2)O(2) exposure, as well as extended male fly lifespan and inhibited Aβ42-induced neurodegeneration in association with decreased caspase activation. Therefore, dTSPO is an essential mediator of apoptosis in Drosophila and plays a central role in controlling longevity and neurodegenerative disease, making it a promising drug target. BlackWell Publishing Ltd 2014-06 2014-02-21 /pmc/articles/PMC4076708/ /pubmed/24977274 http://dx.doi.org/10.1111/acel.12200 Text en © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Original Articles
Lin, Ran
Angelin, Alessia
Da Settimo, Federico
Martini, Claudia
Taliani, Sabrina
Zhu, Shigong
Wallace, Douglas C
Genetic analysis of dTSPO, an outer mitochondrial membrane protein, reveals its functions in apoptosis, longevity, and Aβ42-induced neurodegeneration
title Genetic analysis of dTSPO, an outer mitochondrial membrane protein, reveals its functions in apoptosis, longevity, and Aβ42-induced neurodegeneration
title_full Genetic analysis of dTSPO, an outer mitochondrial membrane protein, reveals its functions in apoptosis, longevity, and Aβ42-induced neurodegeneration
title_fullStr Genetic analysis of dTSPO, an outer mitochondrial membrane protein, reveals its functions in apoptosis, longevity, and Aβ42-induced neurodegeneration
title_full_unstemmed Genetic analysis of dTSPO, an outer mitochondrial membrane protein, reveals its functions in apoptosis, longevity, and Aβ42-induced neurodegeneration
title_short Genetic analysis of dTSPO, an outer mitochondrial membrane protein, reveals its functions in apoptosis, longevity, and Aβ42-induced neurodegeneration
title_sort genetic analysis of dtspo, an outer mitochondrial membrane protein, reveals its functions in apoptosis, longevity, and aβ42-induced neurodegeneration
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076708/
https://www.ncbi.nlm.nih.gov/pubmed/24977274
http://dx.doi.org/10.1111/acel.12200
work_keys_str_mv AT linran geneticanalysisofdtspoanoutermitochondrialmembraneproteinrevealsitsfunctionsinapoptosislongevityandab42inducedneurodegeneration
AT angelinalessia geneticanalysisofdtspoanoutermitochondrialmembraneproteinrevealsitsfunctionsinapoptosislongevityandab42inducedneurodegeneration
AT dasettimofederico geneticanalysisofdtspoanoutermitochondrialmembraneproteinrevealsitsfunctionsinapoptosislongevityandab42inducedneurodegeneration
AT martiniclaudia geneticanalysisofdtspoanoutermitochondrialmembraneproteinrevealsitsfunctionsinapoptosislongevityandab42inducedneurodegeneration
AT talianisabrina geneticanalysisofdtspoanoutermitochondrialmembraneproteinrevealsitsfunctionsinapoptosislongevityandab42inducedneurodegeneration
AT zhushigong geneticanalysisofdtspoanoutermitochondrialmembraneproteinrevealsitsfunctionsinapoptosislongevityandab42inducedneurodegeneration
AT wallacedouglasc geneticanalysisofdtspoanoutermitochondrialmembraneproteinrevealsitsfunctionsinapoptosislongevityandab42inducedneurodegeneration