Abstract
Autophagy is an evolutionarily conserved process that contributes to maintain cell homeostasis. Although it is strongly regulated by many extracellular factors, induction of autophagy is mainly produced by starvation of nutrients. In mammalian cells, the regulation of autophagy by amino acids, and also by the hormone insulin, has been extensively investigated, but knowledge about the effects of other autophagy regulators, including another nutrient, glucose, is more limited. Here we will focus on the signalling pathways by which environmental glucose directly, i.e., independently of insulin and glucagon, regulates autophagy in mammalian cells, but we will also briefly mention some data in yeast. Although glucose deprivation mainly induces autophagy via AMPK activation and the subsequent inhibition of mTORC1, we will also comment other signalling pathways, as well as evidences indicating that, under certain conditions, autophagy can be activated by glucose. A better understanding on how glucose regulates autophagy not only will expand our basic knowledge of this important cell process, but it will be also relevant to understand common human disorders, such as cancer and diabetes, in which glucose levels play an important role.
Highlights
Autophagy is the process by which lysosomes degrade organelles and cellular components
HeLa cells, which do not express LKB1, show low levels of both total and phosphorylated p27 KIP1, even upon glucose starvation. Reconstitution of these cells with LKB1 produces an increase in both total and P-T198 p27KIP1 levels in glucose free medium, as well as in ACC phosphorylation [50]. All these results suggest that p27KIP1 is activated by LKB1/AMP-activated protein kinase (AMPK) during glucose deprivation
In addition to the signalling pathways related with energy changes and reactive oxygen species (ROS) induction that appear to be implicated in the regulation of autophagy in response to glucose levels, there are others implicated in this regulation
Summary
Autophagy is the process by which lysosomes degrade organelles and cellular components. The most important form of autophagy is macroautophagy, in which cytoplasmic components are surrounded by a double membrane, forming an autophagosome. Microautophagy, a still poorly characterized type of autophagy in mammalian cells, consists in the direct engulfment of cytoplasmic components in intralysosomal tubules and vesicles, which are produced by various modifications of the lysosomal membranes. Chaperone-mediated autophagy is a selective lysosomal pathway for the degradation of cytosolic proteins with KFERQ-like sequences, in which both cytosolic and lysosomal chaperones facilitate the transport of these proteins for degradation into the lysosomal lumen through a multimer of the lysosomal protein LAMP2A spanning the lysosomal membrane. We aim to present an overview of what is known on the signalling pathways that regulate autophagy in response to glucose or glucose-deprivation. We will mainly concentrate on mammalian cells, but first we will give a brief and general account on this subject in yeast
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