Abstract
Eukaryotic cells have developed mechanisms that allow them to link growth and proliferation to the availability of energy and biomolecules. AMPK (adenosine monophosphate-activated protein kinase) is one of the most important molecular energy sensors in eukaryotic cells. AMPK activity is able to control a wide variety of metabolic processes connecting cellular metabolism with energy availability. Autophagy is an evolutionarily conserved catabolic pathway whose activity provides energy and basic building blocks for the synthesis of new biomolecules. Given the importance of autophagic degradation for energy production in situations of nutrient scarcity, it seems logical that eukaryotic cells have developed multiple molecular links between AMPK signaling and autophagy regulation. In this review, we will discuss the importance of AMPK activity for diverse aspects of cellular metabolism, and how AMPK modulates autophagic degradation and adapts it to cellular energetic status. We will explain how AMPK-mediated signaling is mechanistically involved in autophagy regulation both through specific phosphorylation of autophagy-relevant proteins or by indirectly impacting in the activity of additional autophagy regulators.
Highlights
Eukaryotic cells are able to adapt to adverse fluctuations in the cellular environment
We describe the main metabolic regulatory functions of AMPK, including its prominent role in autophagy regulation
In parallel to its inhibitory role for lipid synthesis, AMPK activity contributes to ATP generation through the modulation of a variety catabolic and anabolic pathways involved in glucose metabolism [37]
Summary
Eukaryotic cells are able to adapt to adverse fluctuations in the cellular environment. In 1981, the role for AMPK yeast ortholog, SNF1 (Sucrose Non-fermenting 1) as the main energy sensor in this organism was described [1] This kinase is responsible for activating alternate metabolic pathways when the main carbon or nitrogen sources change, adapting cellular metabolism to oscillations in the cellular environment. Autophagy plays essential roles in all eukaryotic cells and has been implicated in multiple processes, such as cell differentiation, cell death, and regulation of innate and adaptive immune responses or antigen presentation, among many other processes in high eukaryotes [10,11] Despite all these functions, autophagy’s most evolutionarily conserved role, from yeast to mammals, is to sustain energy balance in the cell by providing ATP and building blocks (lipids, amino acids, nucleotides, etc.) out of the degradation of non-essential or damaged cellular structures. We will discuss how AMPK activity is key to the coordination of catabolic pathways which produce energy and micro-molecules with anabolic processes, which use energy and micro-molecules to synthesize new macro-molecules which may be essential to sustain cell viability when cells face significant alterations in the intracellular/extracellular environment
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