Beclin 1 interactome controls the crosstalk between apoptosis, autophagy and inflammasome activation: Impact on the aging process

详细信息    查看全文

• 作者：Antero Salminen^a ; ^b ; ^{antero.salminen@uef.fi} ; Kai Kaarniranta^c ; ^d ; ^{kai.kaarniranta@uef.fi} ; Anu Kauppinen^c ; ^{anu.kauppinen@uef.fi}
• 关键词：AIM2 ; absent in melanoma 2 ; AMBRA1 ; activating molecule in Beclin 1-regulated autophagy ; AMPK ; AMP-activated protein kinase ; AP-1 ; activator protein-1 ; APP ; amyloid-¦Â precursor protein ; ARF ; alternate reading frame of the INK4a/ARF locus p14 ; ASC ; apopto
• 刊名：Ageing Research Reviews
• 出版年：2013
• 出版时间：March, 2013
• 年：2013
• 卷：12
• 期：2
• 页码：520-534
• 全文大小：860 K

文摘

Autophagy and apoptosis are crucial cellular housekeeping and tissue survival mechanisms. There is emerging evidence of important crosstalk between apoptosis and autophagy which can be linked to inflammasome activation. Beclin 1 is a platform protein which assembles an interactome consisting of diverse proteins which control the initiation of autophagocytosis and distinct phases in endocytosis. Recent studies have demonstrated that the anti-apoptotic Bcl-2 family members can interact with Beclin 1 and inhibit autophagy. Consequently, impaired autophagy can trigger inflammasome activation. Interestingly, the hallmarks of the ageing process include a decline in autophagy, increased resistance to apoptosis and a low-grade inflammatory phenotype. Age-related stresses, e.g. genotoxic, metabolic and environmental insults, enhance the expression of NF-¦ÊB-driven anti-apoptotic Bcl-2 proteins which repress the Beclin 1-dependent autophagy. Suppression of autophagocytosis provokes inflammation including NF-¦ÊB activation which further potentiates anti-apoptotic defence. In a context-dependent manner, this feedback defence mechanism can enhance the aging process or provoke tumorigenesis or cellular senescence. We will review the role of Beclin 1 interactome in the crosstalk between apoptosis, autophagy and inflammasomes emphasizing that disturbances in Beclin 1-dependent autophagy can have a crucial impact on the aging process.