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2016 ; 12
(4
): 619-31
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A lysosome-centered view of nutrient homeostasis
#MMPMID27050453
Mony VK
; Benjamin S
; O'Rourke EJ
Autophagy
2016[]; 12
(4
): 619-31
PMID27050453
show ga
Lysosomes are highly acidic cellular organelles traditionally viewed as sacs of
enzymes involved in digesting extracellular or intracellular macromolecules for
the regeneration of basic building blocks, cellular housekeeping, or pathogen
degradation. Bound by a single lipid bilayer, lysosomes receive their substrates
by fusing with endosomes or autophagosomes, or through specialized translocation
mechanisms such as chaperone-mediated autophagy or microautophagy. Lysosomes
degrade their substrates using up to 60 different soluble hydrolases and release
their products either to the cytosol through poorly defined exporting and efflux
mechanisms or to the extracellular space by fusing with the plasma membrane.
However, it is becoming evident that the role of the lysosome in nutrient
homeostasis goes beyond the disposal of waste or the recycling of building
blocks. The lysosome is emerging as a signaling hub that can integrate and relay
external and internal nutritional information to promote cellular and organismal
homeostasis, as well as a major contributor to the processing of energy-dense
molecules like glycogen and triglycerides. Here we describe the current knowledge
of the nutrient signaling pathways governing lysosomal function, the role of the
lysosome in nutrient mobilization, and how lysosomes signal other organelles,
distant tissues, and even themselves to ensure energy homeostasis in spite of
fluctuations in energy intake. At the same time, we highlight the value of
genomics approaches to the past and future discoveries of how the lysosome
simultaneously executes and controls cellular homeostasis.