Cetrullo Silvia, D'Adamo Stefania, Tantini Benedetta, Borzi Rosa Maria, Flamigni Flavio
Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, Bologna, Italy.
Laboratorio di Immunoreumatologia e Rigenerazione Tessutale, Istituto Ortopedico Rizzoli, Bologna, Italy; Dipartimento RIT, Laboratorio RAMSES, Istituto Ortopedico Rizzoli, Bologna, Italy.
Crit Rev Eukaryot Gene Expr. 2015;25(1):59-75. doi: 10.1615/critreveukaryotgeneexpr.2015012975.
Cells adapt their metabolism and activities in response to signals from their surroundings, and this ability is essential for their survival in the face of environmental changes. In mammalian tissues a deficit of these mechanisms is commonly associated with cellular aging and degenerative diseases related to aging, such as cardiovascular disease, cancer, immune system decline, and neurological pathologies. Several proteins have been identified as able to respond directly to energy, nutrient, and growth factor levels and stress stimuli in order to mediate adaptations in the cell. Many of these proteins are enzymes that positively or negatively modulate the autophagic process. This review focuses on biochemical mechanisms involving enzymes--specifically, mTOR, AMPK, and Sirt1--that are currently considered important for these adaptive responses, providing an overview of the interactions of the main players in this process.
细胞会根据来自周围环境的信号来调整其新陈代谢和活动,这种能力对于它们在面对环境变化时的生存至关重要。在哺乳动物组织中,这些机制的缺陷通常与细胞衰老以及与衰老相关的退行性疾病有关,如心血管疾病、癌症、免疫系统衰退和神经病理学。已经鉴定出几种蛋白质能够直接响应能量、营养物质、生长因子水平和应激刺激,从而介导细胞的适应性变化。其中许多蛋白质是对自噬过程进行正向或负向调节的酶。本综述重点关注涉及酶(具体而言,是mTOR、AMPK和Sirt1)的生化机制,这些酶目前被认为对这些适应性反应很重要,并概述了这一过程中主要参与者之间的相互作用。