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

Aging Cell

Ran Lin¹  Alessia Angelin³  Federico Da Settimo²  Claudia Martini²  Sabrina Taliani²  Shigong Zhu¹ 

[1] Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China;Dipartimento di Farmacia, Università di Pisa, Pisa, Italy;Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia Research Institute, Philadelphia, PA, USA

关键词: apoptosis;    Drosophila;    longevity;    mitochondria;    neurodegeneration;    TSPO;   

DOI  :  10.1111/acel.12200

来源: Wiley

【 摘 要 】

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 H₂O₂ 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.

【 授权许可】

CC BY   
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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