Open AccessGenetic analysis of dTSPO , an outer mitochondrial membrane protein, reveals its functions in apoptosis, longevity, and Aβ42‐induced neurodegeneration
Author(s) -
Lin Ran,
Angelin Alessia,
Da Settimo Federico,
Martini Claudia,
Taliani Sabrina,
Zhu Shigong,
Wallace Douglas C.
Publication year - 2014
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12200
Subject(s) - biology , neurodegeneration , microbiology and biotechnology , mitochondrion , translocator protein , neuroprotection , apoptosis , gene knockdown , drosophila melanogaster , genetics , gene , pharmacology , disease , immunology , medicine , neuroinflammation , inflammation
Summary 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.