%0 Journal Article
%T Context-Dependent Regulation of Autophagy by IKK-NF-百B Signaling: Impact on the Aging Process
%A Antero Salminen
%A Juha M. T. Hyttinen
%A Anu Kauppinen
%A Kai Kaarniranta
%J International Journal of Cell Biology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/849541
%X The NF-百B signaling system and the autophagic degradation pathway are crucial cellular survival mechanisms, both being well conserved during evolution. Emerging studies have indicated that the IKK/NF-百B signaling axis regulates autophagy in a context-dependent manner. IKK complex and NF-百B can enhance the expression of Beclin 1 and other autophagy-related proteins and stimulate autophagy whereas as a feedback response, autophagy can degrade IKK components. Moreover, NF-百B signaling activates the expression of autophagy inhibitors (e.g., A20 and Bcl-2/xL) and represses the activators of autophagy (BNIP3, JNK1, and ROS). Several studies have indicated that NF-百B signaling is enhanced both during aging and cellular senescence, inducing a proinflammatory phenotype. The aging process is also associated with a decline in autophagic degradation. It seems that the activity of Beclin 1 initiation complex could be impaired with aging, since the expression of Beclin 1 decreases as does the activity of type III PI3K. On the other hand, the expression of inhibitory Bcl-2/xL proteins increases with aging. We will review the recent literature on the control mechanisms of autophagy through IKK/NF-百B signaling and emphasize that NF-百B signaling could be a potent repressor of autophagy with ageing. 1. Introduction One part of the aging process involves a decline in cellular housekeeping functions disturbing the maintenance of organism homeostasis [1, 2]. The accumulation of damaged and defective components increases cellular stress, for example, oxidative stress, which activates cellular defence mechanisms including NF-百B signaling pathway and innate immunity system, such as inflammasomes [3每5] (Section 3.1). Aging is associated with a low-grade proinflammatory phenotype which further interferes with housekeeping and cellular homeostasis. Recent studies have indicated that autophagy is a crucial cleansing system preventing inflammation but its capacity clearly declines with aging [6每8]. The NF-百B signaling system and the autophagic degradation pathway have been closely conserved during evolution and emerging studies indicate that these systems have many context-dependent interactions with each other. We will review the recent literature on the control mechanisms of autophagy by NF-百B signaling and particularly we will focus on its context-dependent regulation during the aging process. 1.1. Autophagy By definition, autophagy or autophagocytosis is a cellular self-digestion process involving the uptake of cellular components and organelles for degradation by lysosomal
%U http://www.hindawi.com/journals/ijcb/2012/849541/