title: Beclin 1 interactome controls the crosstalk between apoptosis, autophagy and inflammasome activation: impact on the aging process.
abstract: 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-κB-driven anti-apoptotic Bcl-2 proteins which repress the Beclin 1-dependent autophagy. Suppression of autophagocytosis provokes inflammation including NF-κB 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.
authors.affiliation: Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland. antero.salminen@uef.fi
authors.forename: Antero
authors.initials: A
authors.lastname: Salminen
authors.forename: Kai
authors.initials: K
authors.lastname: Kaarniranta
authors.forename: Anu
authors.initials: A
authors.lastname: Kauppinen
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D016922:Cellular Senescence / Q000502:physiology*; D006801:Humans; D058847:Inflammasomes / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D058847:Inflammasomes; D008565:Membrane Proteins; D016328:NF-kappa B