Lysosomes are cellular
organelleIn cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....
s that contain acid
hydrolaseIn biochemistry, a hydrolase is an enzyme that catalyzes the hydrolysis of a chemical bond. For example, an enzyme that catalyzed the following reaction is a hydrolase:-Nomenclature:...
enzymes to break down waste materials and cellular debris. They are found in animal cells, while in yeast and plants the same roles are performed by lytic
vacuoleA vacuole is a membrane-bound organelle which is present in all plant and fungal cells and some protist, animal and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water containing inorganic and organic molecules including enzymes in solution, though in certain...
s. Lysosomes digest excess or worn-out
organelleIn cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....
s, food particles, and engulf
virusA virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es or
bacteriaBacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
. The
membraneA biological membrane or biomembrane is an enclosing or separatingmembrane that acts as a selective barrier, within or around a cell. It consists of a lipid bilayer with embedded proteins that may constitute close to 50% of membrane content...
around a lysosome allows the
digestive enzyme'Digestive enzymes' are enzymes that break down polymeric macromolecules into their smaller building blocks, in order to facilitate their absorption by the body. Digestive enzymes are found in the digestive tract of animals where they aid in the digestion of food as well as inside the cells,...
s to work at the 4.5
pHIn chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
they require. Lysosomes fuse with
vacuoleA vacuole is a membrane-bound organelle which is present in all plant and fungal cells and some protist, animal and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water containing inorganic and organic molecules including enzymes in solution, though in certain...
s and dispense their enzymes into the
vacuoleA vacuole is a membrane-bound organelle which is present in all plant and fungal cells and some protist, animal and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water containing inorganic and organic molecules including enzymes in solution, though in certain...
s, digesting their contents. They are created by the addition of hydrolytic enzymes to early
endosomeIn biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for...
s from the
Golgi apparatusThe Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
. The name
lysosome derives from the Greek words
lysisLysis refers to the breaking down of a cell, often by viral, enzymic, or osmotic mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a "lysate"....
,
to separate, and
soma,
body. They are frequently nicknamed "suicide-bags" or "suicide-sacs" by cell biologists due to their role in autolysis. Lysosomes were discovered by the Belgian cytologist
Christian de DuveChristian René, viscount de Duve is a Nobel Prize-winning cytologist and biochemist. De Duve was born in Thames Ditton, Surrey, Great Britain, as a son of Belgian refugees. They returned to Belgium in 1920...
in the 1960s.
The size of lysosomes varies from 0.1–1.2
μmA micrometer , is by definition 1×10-6 of a meter .In plain English, it means one-millionth of a meter . Its unit symbol in the International System of Units is μm...
. At
pHIn chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
4.8, the interior of the lysosomes is acidic compared to the slightly alkaline
cytosolThe cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
(pH 7.2). The lysosome maintains this pH differential by pumping
protonThe proton is a subatomic particle with the symbol or and a positive electric charge of 1 elementary charge. One or more protons are present in the nucleus of each atom, along with neutrons. The number of protons in each atom is its atomic number....
s (H
+ ions) from the cytosol across the
membraneThe cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
via
proton pumpA proton pump is an integral membrane protein that is capable of moving protons across a cell membrane, mitochondrion, or other organelle. Mechanisms are based on conformational changes of the protein structure or on the Q cycle.-Function:...
s and chloride
ion channelIon channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s. The lysosomal membrane protects the cytosol, and therefore the rest of the
cellThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
, from the
degradative enzymeDegradative enzyme is an enzyme which degrades biological molecules. Some examples of degradative enzymes:*Lipase, which digests lipids,*Carbohydrases, which digest carbohydrates ,*Proteases, which digest proteins,...
s within the lysosome. The cell is additionally protected from any lysosomal acid hydrolases that drain into the cytosol, as these enzymes are pH-sensitive and do not function well or at all in the alkaline environment of the cytosol.This ensures that cytosolic molecules and organelles are not lysed in case there is leakage of the hydrolytic enzymes from the lysosome.
Enzymes
Some important enzymes found within lysosomes include:
- Lipase
A lipase is an enzyme that catalyzes the formation or cleavage of fats . Lipases are a subclass of the esterases.Lipases perform essential roles in the digestion, transport and processing of dietary lipids in most, if not all, living organisms...
, which digests lipidLipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s
- Amylase
Amylase is an enzyme that catalyses the breakdown of starch into sugars. Amylase is present in human saliva, where it begins the chemical process of digestion. Food that contains much starch but little sugar, such as rice and potato, taste slightly sweet as they are chewed because amylase turns...
, which digests amyloseAmylose is a linear polymer made up of D-glucose units.This polysaccharide is one of the two components of starch, making up approximately 2-30% of the structure...
, starchStarch or amylum is a carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds. This polysaccharide is produced by all green plants as an energy store...
, and maltodextrins
- Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
s, which digest proteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s
- Nuclease
A nuclease is an enzyme capable of cleaving the phosphodiester bonds between the nucleotide subunits of nucleic acids. Older publications may use terms such as "polynucleotidase" or "nucleodepolymerase"....
s, which digest nucleic acidNucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...
s
- Phosphoric acid
Phosphoric acid, also known as orthophosphoric acid or phosphoric acid, is a mineral acid having the chemical formula H3PO4. Orthophosphoric acid molecules can combine with themselves to form a variety of compounds which are also referred to as phosphoric acids, but in a more general way...
monoesters.
Lysosomal enzymes are synthesized in the cytoplasm and the
endoplasmic reticulumThe endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
, where they receive a
mannose-6-phosphateMannose is a sugar monomer of the aldohexose series of carbohydrates. Mannose is a C-2 epimer of glucose. It is not part of human metabolism, but is a component of microbial cell walls, and is therefore a target of the immune system and also of antibiotics....
tag that targets them for the lysosome . Aberrant lysosomal targeting causes inclusion-cell disease, whereby enzymes do not properly reach the lysosome, resulting in accumulation of waste within these organelles.
Functions
Lysosomes are the cell's waste disposal system and can digest some compounds. They are used for the digestion of
macromoleculeA macromolecule is a very large molecule commonly created by some form of polymerization. In biochemistry, the term is applied to the four conventional biopolymers , as well as non-polymeric molecules with large molecular mass such as macrocycles...
s from
phagocytosis (ingestion of other dying cells or larger extracellular material, like foreign invading microbes),
endocytosisEndocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
(where
receptor proteinIn biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
s are recycled from the cell surface), and
autophagyIn cell biology, autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell's own components through the lysosomal machinery. It is a tightly regulated process that plays a normal part in cell growth, development, and homeostasis, helping to maintain a balance...
(where in old or unneeded organelles or proteins, or microbes that have invaded the cytoplasm are delivered to the lysosome). Autophagy may also lead to
autophagic cell deathIn cell biology, autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell's own components through the lysosomal machinery. It is a tightly regulated process that plays a normal part in cell growth, development, and homeostasis, helping to maintain a balance...
, a form of
programmed self-destructionProgrammed cell-death is death of a cell in any form, mediated by an intracellular program. PCD is carried out in a regulated process which generally confers advantage during an organism's life-cycle...
, or autolysis, of the cell, which means that the cell is digesting itself.
Other functions include digesting foreign bacteria (or other forms of waste) that invade a cell and helping repair damage to the plasma membrane by serving as a membrane patch, sealing the wound. In the past, lysosomes were thought to kill cells that are no longer wanted, such as those in the tails of
tadpoleA tadpole or polliwog is the wholly aquatic larval stage in the life cycle of an amphibian, particularly that of a frog or toad.- Appellation :...
s or in the web from the fingers of a 3- to 6-month-old
fetusA fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
.
Clinical relevance
There are a number of
lysosomal storage diseases that are caused by the malfunction of the lysosomes or one of their digestive proteins; examples include Niemann Pick Type C,
Tay-Sachs diseaseTay–Sachs disease is an autosomal recessive genetic disorder...
and Pompe's disease. These diseases are caused by a defective or missing digestive protein, which leads to the accumulation of substrates within the cell, impairing
metabolismMetabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
.
In the broad sense, these can be classified as
mucopolysaccharidosesMucopolysaccharidoses are a group of metabolic disorders caused by the absence or malfunctioning of lysosomal enzymes needed to break down molecules called glycosaminoglycans - long chains of sugar carbohydrates in each of our cells that help build bone, cartilage, tendons, corneas, skin and...
, GM
2 gangliosidoses,
lipid storage disorderLipid storage disorders are a group of inherited metabolic disorders in which harmful amounts of lipids accumulate in some of the body’s cells and tissues. People with these disorders either do not produce enough of one of the enzymes needed to metabolize lipids or they produce enzymes that do...
s,
glycoproteinosesGlycoproteinosis are lysosomal storage diseases affecting glycoproteins, resulting from defects in lysosomal function. The term is sometimes reserved for conditions involving degradation of glycoproteins.-Types:...
,
mucolipidosesMucolipidosis is a group of inherited metabolic disorders that affect the body's ability to carry out the normal turnover of various materials within cells....
, or
leukodystrophiesLeukodystrophy refers to a group of disorders characterized by dysfunction of the white matter of the brain. The leukodystrophies are caused by imperfect growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers...
.
Lysosomotropism
Weak
basesFor the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...
with lipophilic properties accumulate in acidic intracellular compartments like lysosomes. While the plasma and lysosomal membranes are permeable for neutral and uncharged species of weak bases, the charged protonated species of weak bases do not permeate biomembranes and accumulate within lysosomes. The concentration within lysosomes may reach levels 100 to 1000 fold higher than extracellular concentrations. This phenomenon is called "lysosomotropism" or "acid trapping". The amount of accumulation of lysosomotropic compounds may be estimated using a cell based mathematical model.
A significant part of the clinically approved drugs are lipophilic weak bases with lysosomotropic properties. This explaines a number of pharmacological properties of these drugs, such as high tissue-to-blood concentration gradients or long tissue elimination half-lifes; these properties have been found for drugs such as
haloperidolHaloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
,
levomepromazineLevomepromazine in Germany and Methotrimeprazine in America is an aliphatic phenothiazine neuroleptic drug...
and
amantadineAmantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...
. However, in addition to lysosomotropism, high tissue concentrations and long elimination half-life is explained also by lipophilicity and absorption of drugs to fatty tissue structures. Important lysosomal enzymes, such as acid sphingomyelinase, may be inhibited by lysososomally accumulated drugs. Such compounds are termed FIASMAs (functional inhibitor of acid sphingomyelinase) and include for example
fluoxetineFluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
,
sertralineSertraline hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor class. It was introduced to the market by Pfizer in 1991. Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive–compulsive, panic, and social anxiety disorders in...
or
amitriptylineAmitriptyline is a tricyclic antidepressant . It is the most widely used TCA and has at least equal efficacy against depression as the newer class of SSRIs...
.
External links