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A lysosome-centered view of nutrient homeostasis.

Mony VK, Benjamin S, O'Rourke EJ - Autophagy (2016)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: a Department of Biology , College of Arts and Sciences, University of Virginia , Charlottesville , VA , USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

The lysosome is a nutrient sensing, processing and signaling center. The lysosome is the only organelle that receives nutrients and nutritional information from the cell (autophagy) and from the environment (endocytosis). Some of the roles of the lysosome in nutrient homeostasis include: I) sensing of nutrients and growth factors by the Lysosome Nutrient Sensing (LYNUS) machinery, II) digestion and recycling of circulating nutrients (i.e., cholesterol), growth factors (i.e., GH1 [growth hormone 1]), and nutrient regulators (i.e., perilipins); III) digestion and recycling of intracellular macromolecules and organelles; IV) recycling of growth factors, growth factor receptors (i.e., for GH1 and insulin), and nutrient receptors (i.e., LDLR/LDL receptor), V) coordination of responses to fluctuations in nutrient availability by releasing signaling molecules that activate homeostatic responses (i.e., cholesterol biosynthesis or activation of autophagy) locally and in distant cells and tissues; VI) controlling its own biogenesis, and VII) storage. All together, these functions provide building blocks and energy units to promote growth and reproduction, but most importantly the lysosome integrates nutritional information from the cell and the environment so that growth and reproduction are only promoted when conditions are favorable to do so.
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f0003: The lysosome is a nutrient sensing, processing and signaling center. The lysosome is the only organelle that receives nutrients and nutritional information from the cell (autophagy) and from the environment (endocytosis). Some of the roles of the lysosome in nutrient homeostasis include: I) sensing of nutrients and growth factors by the Lysosome Nutrient Sensing (LYNUS) machinery, II) digestion and recycling of circulating nutrients (i.e., cholesterol), growth factors (i.e., GH1 [growth hormone 1]), and nutrient regulators (i.e., perilipins); III) digestion and recycling of intracellular macromolecules and organelles; IV) recycling of growth factors, growth factor receptors (i.e., for GH1 and insulin), and nutrient receptors (i.e., LDLR/LDL receptor), V) coordination of responses to fluctuations in nutrient availability by releasing signaling molecules that activate homeostatic responses (i.e., cholesterol biosynthesis or activation of autophagy) locally and in distant cells and tissues; VI) controlling its own biogenesis, and VII) storage. All together, these functions provide building blocks and energy units to promote growth and reproduction, but most importantly the lysosome integrates nutritional information from the cell and the environment so that growth and reproduction are only promoted when conditions are favorable to do so.

Mentions: We have described the role of the lysosome in: 1) nutrient sensing, 2) processing of energy-dense nutrients, and 3) the emission of signals that distally control or modulate energy homeostasis (Fig. 3). The critical role of the lysosome in ensuring organismal homeostasis is made evident by the striking conservation of its regulation and function. Comprehensive understanding of the role of the lysosome in essential biological functions, such as growth and reproduction, and in human disease requires broad approaches. Genomics, transcriptomics, proteomics, and lipidomics of patient-derived samples may reveal variations in sequence, expression, and activity of lysosomal proteins as well as its derived metabolites. These variants may either have predisposing, protective, or no effect on disease onset or progression. Therefore, functional genomics approaches in simpler model systems may help elucidate how these variants, and others too disruptive to be found in human populations, affect how the lysosome senses, processes, and relays information, and ultimately defines organismal homeostasis.Figure 3.


A lysosome-centered view of nutrient homeostasis.

Mony VK, Benjamin S, O'Rourke EJ - Autophagy (2016)

The lysosome is a nutrient sensing, processing and signaling center. The lysosome is the only organelle that receives nutrients and nutritional information from the cell (autophagy) and from the environment (endocytosis). Some of the roles of the lysosome in nutrient homeostasis include: I) sensing of nutrients and growth factors by the Lysosome Nutrient Sensing (LYNUS) machinery, II) digestion and recycling of circulating nutrients (i.e., cholesterol), growth factors (i.e., GH1 [growth hormone 1]), and nutrient regulators (i.e., perilipins); III) digestion and recycling of intracellular macromolecules and organelles; IV) recycling of growth factors, growth factor receptors (i.e., for GH1 and insulin), and nutrient receptors (i.e., LDLR/LDL receptor), V) coordination of responses to fluctuations in nutrient availability by releasing signaling molecules that activate homeostatic responses (i.e., cholesterol biosynthesis or activation of autophagy) locally and in distant cells and tissues; VI) controlling its own biogenesis, and VII) storage. All together, these functions provide building blocks and energy units to promote growth and reproduction, but most importantly the lysosome integrates nutritional information from the cell and the environment so that growth and reproduction are only promoted when conditions are favorable to do so.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836021&req=5

f0003: The lysosome is a nutrient sensing, processing and signaling center. The lysosome is the only organelle that receives nutrients and nutritional information from the cell (autophagy) and from the environment (endocytosis). Some of the roles of the lysosome in nutrient homeostasis include: I) sensing of nutrients and growth factors by the Lysosome Nutrient Sensing (LYNUS) machinery, II) digestion and recycling of circulating nutrients (i.e., cholesterol), growth factors (i.e., GH1 [growth hormone 1]), and nutrient regulators (i.e., perilipins); III) digestion and recycling of intracellular macromolecules and organelles; IV) recycling of growth factors, growth factor receptors (i.e., for GH1 and insulin), and nutrient receptors (i.e., LDLR/LDL receptor), V) coordination of responses to fluctuations in nutrient availability by releasing signaling molecules that activate homeostatic responses (i.e., cholesterol biosynthesis or activation of autophagy) locally and in distant cells and tissues; VI) controlling its own biogenesis, and VII) storage. All together, these functions provide building blocks and energy units to promote growth and reproduction, but most importantly the lysosome integrates nutritional information from the cell and the environment so that growth and reproduction are only promoted when conditions are favorable to do so.
Mentions: We have described the role of the lysosome in: 1) nutrient sensing, 2) processing of energy-dense nutrients, and 3) the emission of signals that distally control or modulate energy homeostasis (Fig. 3). The critical role of the lysosome in ensuring organismal homeostasis is made evident by the striking conservation of its regulation and function. Comprehensive understanding of the role of the lysosome in essential biological functions, such as growth and reproduction, and in human disease requires broad approaches. Genomics, transcriptomics, proteomics, and lipidomics of patient-derived samples may reveal variations in sequence, expression, and activity of lysosomal proteins as well as its derived metabolites. These variants may either have predisposing, protective, or no effect on disease onset or progression. Therefore, functional genomics approaches in simpler model systems may help elucidate how these variants, and others too disruptive to be found in human populations, affect how the lysosome senses, processes, and relays information, and ultimately defines organismal homeostasis.Figure 3.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: a Department of Biology , College of Arts and Sciences, University of Virginia , Charlottesville , VA , USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus