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Critical Reviews™ in Eukaryotic Gene Expression

Impact factor: 1.660

ISSN Print: 1045-4403
ISSN Online: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukaryotGeneExpr.2015012975
pages 59-75

mTOR, AMPK, and Sirt1: Key Players in Metabolic Stress Management

Silvia Cetrullo
Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, Bologna, Italy
Stefania D'Adamo
Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, Bologna, Italy
Benedetta Tantini
Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, Bologna, Italy
Rosa Maria Borzi
Laboratorio di Immunoreumatologia e Rigenerazione Tessutale, Istituto Ortopedico Rizzoli, Bologna, Italy; Dipartimento RIT, Laboratorio RAMSES, Istituto Ortopedico Rizzoli, Bologna, Italy
Flavio Flamigni
Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, Bologna, Italy

ABSTRACT

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.

KEY WORDS: mTOR, AMPK, Sirt1, autophagy