Lysosomes

Feroze N. Ghadially MB BS (Bom.), MB BS (Lond.), MD, PhD, DSc (Lond.), Hon. DSc (Guelph), FRCPath., FRCP(C), FRSA , in Ultrastructural Pathology of the Cell and Matrix (Third Edition), 1988

Publisher Summary

The term lysosome is used to describe a group of membrane-bound particles that contain acid hydrolases. These organelles are considered to be the main part of an intracellular digestive system, sometimes referred to as the vacuome or vacuolar apparatus, and are capable of digesting or degrading a variety of endogenous and exogenous substances. The other parts of the system include structures such as pinocytotic and micropinocytotic vesicles and phagocytic vacuoles that transport exogenous substances into the cell. Many functional and morphological forms of lysosomes have been identified and named. One such is the primary lysosome also called the true, pure, or original lysosome. The primary lysosomes, however derived, contain hydrolytic enzymes but no substrate to act upon. Structures in which the enzymes confront substrates and digestion ensues are the secondary lysosomes. There are two types of secondary lysosomes—heterolysosomes and autolysosomes. The term residual body, also known as telolysosome, is used to describe late forms of secondary lysosomes. Lipofuscin granules and hemosiderin granules (siderosomes) of light microscopy are regarded as examples of residual bodies. Certain enzymeless members of the vacuolar system are called prelysosomes. It is worth noting that the lysosome concept has played an important role in the understanding of the many physiological and pathological processes.

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Organizational Cell Biology

R. Shrestha , ... D.M. Ward , in Encyclopedia of Cell Biology, 2016

Abstract

Lysosomes are membrane-bound organelles that contain hydrolases capable of degrading proteins, lipids, and carbohydrates. They are involved in nutrient sensing and storage and retrieval. Lysosomes are highly dynamic and are capable of fusion and fission events with other organelles and plasma membrane. Higher eukaryotes possess a specialized group of lysosomes termed secretory lysosomes that are involved in pigmentation, coagulation, wound repair, and immunologic functions. Understanding the molecular machinery that regulates lysosome and secretory lysosome homeostasis is underscored by the fact that mutations in the genes that regulate the biogenesis, movement and delivery of lysosome and secretory lysosome contents result in human diseases.

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Imaging and Spectroscopic Analysis of Living Cells

Paul R. Pryor , in Methods in Enzymology, 2012

Abstract

Lysosomes are an important cellular organelle that receive and degrade macromolecules from the secretory, endocytic, autophagic, and phagocytic membrane-trafficking pathways. Defects in lysosome function lead to the development of disease with often-severe consequences to the individual. Since the discovery of lysosomes by Christian de Duve over 50  years ago, research into endocytic and lysosomal biology has allowed for the development of tools to understand further the role of lysosomes in cells. There are now several fluorescent probes that can be used to visualize and assess membrane traffic to the lysosome as well as probes to assess the activity of lysosomal hydrolases in live cells. This chapter describes the current methods used to measure lysosome function in live cells.

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Role of Autophagy in P2X7 Receptor-Mediated Maturation and Unconventional Secretion of IL-1β in Microglia

Takato Takenouchi , ... Makoto Hashimoto , in Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, 2015

Conventional and Secretory Lysosomes

Lysosomes are membrane-enclosed organelles that function as the digestive system of animal cells, serving both to degrade materials taken up from outside the cells and to digest the cells' own worn-out components. They contain about 50 different degradative enzymes, which can hydrolyze proteins, nucleic acids, carbohydrates, and lipids. These enzymes are acid hydrolases and are active at acidic pH (~5), but not at physiological pH; thus, the interior of lysosomes is acidic (pH 4.8) whereas the cytosol is slightly alkaline (pH 7.2). This pH differential is maintained by pumping H + ions from the cytosol across the lysosomal membrane using proton pumps. Lysosomes are involved in the digestion of macromolecules during endocytosis, phagocytosis, and autophagy.

A specialized class of lysosomes called "secretory lysosomes" has recently been recognized (Blott and Griffiths, 2002). Secretory lysosomes share features with both conventional lysosomes and secretory granules and are abundant in some cell types, such as hematopoietic cells and melanocytes. Macrophages contain abundant secretory lysosomes and utilize them to exert their innate immune functions. Through the exocytosis of secretory lysosomes, they can secrete not only lysosomal enzymes but also antimicrobial proteins and several cytokines. Microglia also contain an abundance of secretory lysosomes, and we observed that P2X7R activation by ATP induced the secretion of the lysosomal enzyme cathepsin D from microglial cells in an extracellular Ca2+-dependent manner (Takenouchi et al., 2009b, 2011). A recent study demonstrated that secretory lysosomes from microglia contain abundant ATP. In addition, they found that ATP-induced ATP secretion via lysosome exocytosis contributes to the regulation of microglial migration in the brain (Dou et al., 2012).

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The Cell: Basic Structure and Function

Magnus von Knebel Doeberitz , Nicolas Wentzensen , in Comprehensive Cytopathology (Third Edition), 2008

Lysosomes

Lysosomes are small vesicles derived from the Golgi apparatus; they contain up to 40 acidic enzymes (hydrolases) at a pH 5. The membrane prevents the aggressive enzymes from destroying cellular structures. Although the contents can vary substantially, there are basically no morphological differences between functionally different lysosomes. The main function of lysosomes is the digestion of internal (non-functional cell organelles) and external (food, bacteria, leukocytes, debris) material. The processed material is either released to the cytoplasm, secreted, or stored in lysosomes.

Several storage diseases (e.g. Hunter-Hurler-Syndrome) are characterized by a deficiency of lysosomal enzymes. These disorders lead to accumulation of incompletely digested mucopolysaccharides in the lysosomes.

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Organizational Cell Biology

M. Fukuda , in Encyclopedia of Cell Biology, 2016

Morphology, Composition, and Function of Lysosome-Related Organelles

Lysosomes are major degradative organelles in eukaryotic cells. Their luminal pH is acidic (~5), and a variety of acid hydrolases in their lumen achieve their degradative function. Lysosomes also contain a unique set of highly glycosylated, lysosome-associated membrane proteins (LAMPs), for example, LAMP-1 and LAMP-2, in their limiting membrane ( Saftig and Klumperman, 2009). Lysosome-related organelles (LROs) are a group of cell-type-specific membrane compartments in metazoans that share several of the above features with lysosomes, including an acidic pH and containing certain LAMPs (Dell'Angelica et al., 2000). Despite the features they share with lysosomes, LROs are highly diversified in terms of morphology and composition and are present in only certain types of highly specialized cells (Raposo et al., 2007) (representative cell-type-specific LROs are summarized in the first and second columns of Table 1). In contrast to the heterogeneous morphology of lysosomes, each LRO exhibits highly specialized morphology, for example, the dense granules and α-granules in platelets are spherical shaped, the same as the conventional secretory vesicles in endocrine cells; the melanosomes in melanocytes are rugby-ball-shaped; the Weibel–Palade bodies (WPBs) in endothelial cells are cigar-shaped; and the MHC (major histocompatibility complex) class II compartments in antigen-presenting cells and lamellar bodies in pulmonary alveolar type II cells have a multilamellar structure (Figure 1). The composition of each LRO is also highly specialized (Table 1, third column) to maintain its unique morphology and to perform specialized functions. Melanosomes contain Pmel17 protein fibrils, on to which melanins are deposited, and WPBs contain von Willebrand factor (vWF) tubules (Figure 1). Because of the differences in structure and composition of LROs, each LRO possess a unique biological function(s) (Table 1, fourth column). The same as lysosomes undergo exocytosis under specialized conditions, for example, during plasma membrane repair, most LROs undergo exocytosis, that is, secretion of the luminal content of the LROs into the extracellular space by fusion between LROs and the plasma membrane, in response to extracellular stimuli, and so these secretory LROs are also called secretory lysosomes (Blott and Griffiths, 2002). The secretory functions of LROs are crucial for many aspects of biological activities in higher animals, including pigmentation (transfer of melanins from melanocytes to keratinocytes), hemostasis (secretion of clotting factors by platelets and endothelial cells), immunity (secretion of perforin and granzymes by cytotoxic T lymphocytes for target cell killing), and lung plasticity (surfactant secretion by alveolar type II cells).

Table 1. Cell-specific LROs and their functions

Organelle Cell type Major content Physiological function
Melanosomes Melanocytes and RPE cells Melanin and melanogenic enzymes Melanin synthesis, storage, and pigmentation
Lytic granules a Cytotoxic T lymphocytes and NK cells Perforin and granzymes Target cell killing
Dense granules a Platelets and megakaryocytes ATP, ADP, and serotonin Blood clotting
α Granules a Platelets and megakaryocytes Fibrinogen, vWF, and P-selectin Platelet adhesion and blood clotting
Basophilic granules a Basophils and mast cells Histamine and serotonin Inflammation
MHC class II compartments a Dendritic cells, B lymphocytes, and macrophages MHC class II Antigen presentation
Azurophilic/primary granules a Neutrophils Myeloperoxidase and defensins Antimicrobial defense
Osteoclast granules a Osteoclasts Lysosomal hydrolyzes Bone resorption and remodeling
Lamellar bodies a Pulmonary alveolar type II cells Surfactant phospholipids Surfactant storage and secretion
Weibel–Palade bodies a Endothelial cells vWF and P-selection Blood clotting and inflammation
Notochord vacuoles Notochord Not identified b Morphogenesis of the body axis and spine
Pigment granules Drosophila melanogaster eye cells Eye pigments Eye pigmentation
Fat storage organelles Caenorhabditis elegans gut cells Lipofuscin Fat storage

Abbreviations: ADP, adenosine diphosphate; ATP, adenosine triphosphate; LROs, lysosome-related organelles; MHC, major histocompatibility complex; NK, natural killer; RPE, retinal pigment epithelial.

Source: Adapted from Raposo, G., Marks, M.S., Cutler D.F., 2007. Lysosome-related organelles: Driving post-Golgi compartments into specialization. Current Opinion in Cell Biology 19, 394–401; Blott, E.J., Griffiths, G.M., 2002. Secretory lysosomes. Nature Reviews Molecular Cell Biology 3, 122–131.

a
Because these lysosome-related organelles undergo exocytosis in a stimulus-dependent manner, they are also called secretory lysososmes. The stimulus for exocytosis varies with the cell types.
b
Notochord vacuoles were assumed to contain glycosaminoglycans, but recent evidence shows that zebrafish notochord vacuoles do not contain glycosaminoglycans.

Figure 1. Unique morphology of LROs. Schematic representation of dense granule and α-granule (both spherical shaped) in platelets (top row); melanosome in melanocytes (rugby-ball-shaped) and WPB (cigar-shaped) in endothelial cells (middle row); and MHC class II compartment (multilamellar structure) in antigen-presenting cells and lamellar body (multilamellar structure) in pulmonary alveolar type II cells (bottom row).

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Role of subcellular organelles: lysosomes

Eric D. Wills , in Biochemical Basis of Medicine, 1985

b Kidney

Lysosomes occur in the endothelial cells of the glomerulus, and in the lining cells of the proximal tubule, loop of Henle, distal tubule and collecting tubule. Lysosomes of all parts of the kidney carry out autophagy of cellular organelles but lysosomes of the proximal tubule are likely to play a special role in heterophagy. In the proximal tubule protein molecules, such as albumin and haemoglobin, that have passed through the glomerulus are absorbed into the lysosomes and degraded by the lysosomal cathepsins. It has been estimated that 10-15 per cent of total serum albumin degradation occurs in the kidney.

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Nanotechnology in Intracellular Trafficking, Imaging, and Delivery of Therapeutic Agents

Animikh Ray , Ashim K. Mitra , in Emerging Nanotechnologies for Diagnostics, Drug Delivery and Medical Devices, 2017

3.5 Lysosomes

Lysosomes are considered to be final organelles in endocytic as well as autophagocytic pathways. These vesicles are the final destination for numerous components [38]. Lysosomes can influence biochemical events such as expression of surface receptors and inhibition of microbial infections [39,40]. Microscopic examinations demonstrate that the structure and volume of lysosomes are nonuniform. The internal environment of lysosomes is acidic in nature with a pH of 4.6–5 [41]. This acidity is created and maintained by numerous H+ ATPases. The lysosomal membrane is degraded following treatment of cells with pH-sensitive chitosan nanoparticles encapsulating methotrexate (MTX). Fig. 8.5 depicts the effect of MTX-loaded nanoparticle on lysosomal membrane. This process has been investigated with acridine orange (AO) relocation technique [42]. While designing nanoformulations, investigators need to be careful that the target of the drug delivery system is not the lysosome. These particles need to undergo endosomal escape before formation of lysosome. Once the nanostructures are engulfed by lysosome the particles are degraded and are unable to deliver their payload if the target is nucleus, mitochondria, or some other organelle.

Figure 8.5. Assessment of the effects of chitosan nanoparticles (NPs) encapsulating methotrexate (MTX) (MTX-CS-NPs) on lysosomal membrane permeabilization in HeLa cells as visualized via AO staining. In untreated control cells, lysosomes can be seen as red–orange granules and cytoplasm shows a diffuse green fluorescence. In cells with lysosomal membrane damage (HeLa cells treated with 50   mg/mL MTX-CS-NPs) is evident [42].

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The Animal Cell

Donald B. McMillan , Richard J. Harris , in An Atlas of Comparative Vertebrate Histology, 2018

Lysosomes

Lysosomes are dense bodies in the cytoplasm, which were originally defined biochemically as being limited by a membrane and containing acid hydrolases (hydrolytic enzymes that function in slightly acid conditions) ( Figs. A49 and A50). The structures identified in electron micrographs that fulfill these criteria are diverse and may be spherical, ovoid, or irregular in outline, with a pale to dense matrix of varying degrees of homogeneity. Identification of lysosomes in electron micrographs is unreliable and should be verified by other means such as their uptake of certain fluorescent dyes (e.g., acridine orange) as observed under ultraviolet light and by their histochemical reactions for acid hydrolases.

Figure A49. Liver cell of a rat. The large dense bodies in this micrograph are lysosomes; the small dense bodies peppered throughout are granules of glycogen. Both granular and agranular endoplasmic reticulum and mitochondria may be recognized. There is a Golgi complex in the upper left corner. A small amount of the nucleus lurks at the lower left. Lysosomes contain portions of cytoplasmic components such as glycogen, mitochondria, or cisternae of the endoplasmic reticulum. Hydrolytic enzymes (phosphatases and proteases) provide intracellular digestion of worn-out cellular organelles and materials taken into the cell by endocytosis. 30,000×.

Figure A50. The synthesis and fate of lysosomes. primary lysosomes are formed from the Golgi sacs. When they fuse with a substance to be digested they become secondary lysosomes. They may digest materials absorbed from outside the cell by phagocytosis and become phagosomes. They may absorb worn-out organelles within the cell and become autophagic vacuoles. residual bodies are lysosomes containing undigested material.

Lysosomes assist in the intracellular digestion of worn-out cellular organelles and materials taken into the cell by endocytosis. The indigestible residues accumulate in the cell as lipofuscin granules, the "age pigments" or "wear and tear pigments" (Fig. A51). The hydrolytic enzymes of the lysosomes are normally safely contained within the membrane but may be released and cause breakdown of injured cells.

Figure A51. Granules of the brownish pigment lipofuscin have accumulated in the cytoplasm of a neuron in this mammalian spinal ganglion. 63×.

Lysosomes are formed from the Golgi sacs (Fig. A50). Newly formed lysosomes are primary lysosomes. When they fuse with substances to be digested they become secondary lysosomes; these may be further subdivided on the basis of the material being digested as phagosomes, digestive vacuoles, or autophagic vacuoles. Lysosomes are formed from the inner Golgi sacs which, in turn, are derived from the rough endoplasmic reticulum. These three components are sometimes referred to as the GERL.

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The role of lysosomes in autophagy

Yoana Rabanal-Ruiz , Viktor I. Korolchuk , in Autophagy in Health and Disease (Second Edition), 2022

Lysosome overview

Lysosomes were initially described by Christian de Duve 1 and have classically been considered the primary degradative organelle in eukaryotic cells. 2 Lysosome-mediated catabolic degradation is attributable to more than 60 hydrolases (proteases, lipases, and glycosidases) present within the lysosomal lumen 3 and operating in the acidic environment established by the vacuolar H+-ATPase (v-ATPase) located in the lysosomal membrane. 4 , 5 Other glycosylated membrane proteins that coat the lysosomal membrane regulate transport across the membrane as well as membrane stability. 6

Lysosomes receive extracellular-derived molecular cargo from endocytosis and phagocytosis for degradation. 7 , 8 Intracellular material also reaches the lysosome through a "self-eating" catabolic process known as autophagy wherein cytoplasmic cellular components, such as macromolecules, damaged or misfolded proteins, and entire organelles, are delivered to the lysosome for degradation and recycling. 9 The degradation products generated are transported from the lysosome via specific permeases/exporters. 10–12 Lysosomes also drive various physiological processes including plasma membrane repair, cholesterol transport, metal ion homeostasis, and immune responses. In addition, through a process known as lysosomal exocytosis, lysosomes can fuse with the plasma membrane to secrete their content. 13 These distinctive capabilities establish an essential role for the lysosome in maintaining metabolic homeostasis and cellular health. Indeed, lysosomal dysfunction underlies inherited metabolic diseases called lysosomal storage disorders (LSDs) and characterized by a progressive accumulation of substrates in the lysosomes due to enzyme or permease deficiencies. LSDs are closely associated with an increased risk of neurodegeneration, cardiovascular diseases, age-related diseases, and cancer. 14

In the past few years, the view of lysosomes has progressed from that of a static, degradative system to a key signaling node for cellular adaptation. In this evolving picture governing growth and differentiation, the input of and response to cellular signals such as nutrient, energy, and stress levels are integrated through a network that uses the lysosome as a signaling platform 15 (summarized in Fig. 5.1).

Figure 5.1. Lysosome as a metabolic sensor. The lysosome functions as a key organelle that can sense, integrate, and respond to variations in the levels of amino acids, glucose, cholesterol, energy, or growth factor signals. These responses include autophagy regulation and metabolic adaptation in order to meet cellular demands for nutrients and energy.

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