细胞内的消化系统-溶酶体的主要功能

A Brief Understanding of the Major Functions of Lysosomes

　

 

　

溶酶体（Lysosome)是专门的膜结合囊泡，其含有用于分子消化的酶。由于这些酶，它们在分子的再循环，细胞碎片的处理，细胞膜修复，吞噬作用以及程序性细胞死亡中起主要作用。

 

溶酶体是存在于动物细胞的细胞质中的球形，膜结合的细胞器。植物细胞很少含有溶酶体。 “溶酶体”这个词来源于两个希腊词 - “裂解”（破坏）和“躯体”（身体）。这些球形细胞器由磷脂双层结合，直径约0.2至2μm。这种膜结合的内部pH值为4.8，含有一组称为水解酶的裂解酶，可以集体消化几乎任何类型的大分子。蛋白质，脂质，多糖，DNA，RNA等可以通过这些酶在溶酶体的酸性内部水解。

　

功能

溶酶体是多态的并且作为原代，继发，自噬和分泌性溶酶体存在。不需要的大分子的分解是这些细胞器的主要功能。此外，它们还参与细胞膜修复，并在针对细菌，病毒和其他抗原等异物的免疫应答中发挥重要作用。下面给出了它们在各种细胞过程中所起作用的详细说明。

自噬

自噬是细胞内过程，细胞利用溶酶体机制降解其自身成分并回收分子。受损的大分子，畸形蛋白质，非功能性，长寿命蛋白质以及受损和旧的细胞器都被溶酶体酶分解。在靶组分周围形成磷脂膜，导致形成称为自噬泡的囊泡。然后，这个液泡与初级溶酶体融合，其中水解酶将大分子消化成糖，氨基酸和核苷酸，这是每个细胞的主要构建块。这些有用的消化产物被释放到胞质中并可用于合成新的大分子和细胞器，而不需要的产物在细胞外释放。

此外，在饥饿或营养限制条件下，发生正常细胞器的自噬，从而有助于维持正常细胞过程所需的营养水平。

　

在胞吞作用和吞噬作用中的作用

胞吞作用是细胞摄取外来物质的过程。吞噬作用是一种特殊形式的胞吞作用，其中诸如死细胞，细胞碎片，细菌，病毒等大体被吞噬。摄取通过专门的囊泡发生，所述囊泡与溶酶体融合，然后通过水解酶降解外来实体。这些过程直接或间接地在病原体破坏中起着至关重要的作用。

 

细胞凋亡中的作用

细胞凋亡或程序性细胞死亡是一种非常复杂的细胞自杀机制。这种机制在胚胎发育和破坏旧细胞，感染细胞和DNA损伤的细胞中是必不可少的。细胞凋亡通过细胞中的各种途径启动，其中之一是溶酶体介导的细胞凋亡途径。存在于溶酶体中的某些蛋白酶已被鉴定为这种细胞死亡的引发剂之一。这些蛋白酶导致一系列信号和事件，其特征在于细胞组分的分解。这些成分被包装在称为凋亡小体的囊泡中，所述凋亡小体被相邻细胞吞噬。相邻细胞的溶酶体导致这些组分的残余消化。

　

 

在受精中的作用

溶酶体还能够在细胞外释放其消化酶以引起细胞外消化。在受精过程中，精子的溶酶体内容物被释放到细胞外，以便使卵子周围的限制性膜消化。这有利于精子和卵子的融合。除此之外，一旦两个细胞融合，父系线粒体就会通过卵子的溶酶体机制被破坏。由于精子的高代谢活动，精子衍生的线粒体倾向于积累基因突变。因此，需要从融合细胞中消除它们以避免突变转移到所得胚胎中。

　

细胞膜修复

机械应力和致病作用的条件可导致某些斑块的破坏或细胞膜中孔的形成。分泌的溶酶体在靠近受损斑块的位置与细胞膜融合。这导致细胞外水解酶的释放。在这些水解酶中，称为酸性鞘磷脂酶（ASM）的特化水解酶导致细胞对受损斑块的内化。此外，溶酶体与膜的融合提供额外的脂质并防止细胞边界的收缩。

 

当它们发生故障时

溶酶体功能障碍导致约50种不同类型的罕见遗传性代谢紊乱。新的溶酶体遗传性相关疾病有待确定。

消化酶的缺陷或缺失导致细胞内底物的积累，从而损害新陈代谢。溶酶体酶的这种缺乏或功能障碍导致几种可遗传的代谢紊乱，其统称为溶酶体贮积病。下面给出了这些的一些主要特征。

溶酶体贮积病

溶酶体贮积病的特征在于存在含有累积未消化细胞成分的异常增大的溶酶体。积累的成分或大分子取决于功能失调的特定酶。 Pompe病，Tay-Sachs病，粘多糖病（MPS）和戈谢病就是一些例子。在某些情况下，出生时会出现身材矮小，骨骼畸形，心脏和呼吸困难，头部扩大，肝脏和脾脏等症状。然而，在某些情况下，疾病的发作发生在较晚的年龄，并且各种器官根据疾病的类型而受到影响。预期寿命变化很大，严重形式的人可以在5-10岁之间存活。这些疾病目前无法治愈，可用的治疗方法主要是减轻症状。

　

溶酶体分离细胞中的消化酶并使它们与其他细胞部分隔离。这种称为溶酶体的“细胞内消化系统”在细胞存活和维持细胞完整性中起重要作用。

　

Lysosomes are specialized membrane-bound vesicles that contain enzymes for molecular digestion. Owing to these enzymes, they play a major role in recycling of molecules, disposal of cellular debris, cell membrane repair, phagocytosis as well as programmed cell death.

 

Lysosomes are spherical, membrane-bound organelles present in the cytoplasm of animal cells. Plant cells rarely contain lysosomes. The word 'lysosome' is derived from the two Greek words - 'lysis' (destruction) and 'soma' (body). These spherical organelles are bound by a phospholipid bilayer and are about 0.2 to 2 μm in diameter. This membrane-bound interior has a pH of 4.8 and contains a set of lytic enzymes called hydrolases, which can collectively digest almost any type of macromolecule. Proteins, lipids, polysaccharides, DNA, RNA, etc., can be hydrolyzed by these enzymes inside the acidic interior of the lysosomes.

Functions

Lysosomes are polymorphic and exist as primary, secondary, autophagic and secretory lysosomes. The breakdown of unwanted macromolecules is the main function of these organelles. In addition, they are also involved in cell membrane repair and play a major role in the immune response against foreign bodies like bacteria, viruses and other antigens. A detailed account of the role they play in various cellular processes has been given below.

Autophagy

Autophagy is the intracellular process by which the cell degrades its own components using the lysosomal machinery and recycles the molecules. Damaged macromolecules, malformed proteins, non-functional, long-lived proteins, and damaged and old organelles are all broken down by the lysosomal enzymes. A phospholipid membrane is formed around the target component, resulting in the formation of a vesicle called autophagic vacuole. This vacuole then fuses with the primary lysosome where the hydrolases digest the macromolecules to sugars, amino acids and nucleotides, which are the primary building blocks of every cell. These useful digestion products are released into the cytosol and can be utilized in the synthesis of new macromolecules and organelles, whereas the unwanted products are released outside the cell.

 

Also, during starvation, or nutrient-limiting conditions, autophagy of normal organelles occurs, thus helping to maintain the level of nutrients required for the normal cellular processes.

Role in Endocytosis and Phagocytosis

Endocytosis is the process for cellular uptake of foreign material. Phagocytosis is a specialized form of endocytosis wherein large bodies such as dead cells, cell debris, bacteria, viruses, etc., are engulfed. The uptake occurs through specialized vesicles which fuse with the lysosomes followed by the degradation of the foreign entity by hydrolases. Directly or indirectly, both these processes play a crucial role in pathogen destruction.

　

Role in Apoptosis

Apoptosis or programmed cell death is a very intricately controlled mechanism of cellular suicide. Such a mechanism is essential during embryonic development and for destruction of old cells, infected cells and cells with DNA damage. Apoptosis is initiated through various pathways in a cell, one of them being lysosome-mediated apoptotic pathway. Certain proteases present in lysosomes have been identified as one of the initiators for such cell death. These proteases lead to a series of signals and events characterized by breakdown of the cellular components. These components are packed into vesicles termed apoptotic bodies which are engulfed by neighboring cells. The lysosomes of the neighboring cells bring about the residual digestion of these components.

　

　

　

Role in Fertilization

Lysosomes are also capable of releasing their digestive enzymes outside the cell to bring about extracellular digestion. During fertilization, the lysosomal contents of sperms are released outside the cell in order to bring about the digestion of the limiting membrane around the egg. This facilitates fusion of the sperm and egg. In addition to this, once the two cells fuse, the paternal mitochondria are destroyed through the lysosomal machinery of the egg. Sperm-derived mitochondria tend to accumulate genetic mutations due to the high metabolic activity of sperms. Hence, they need to be eliminated from the fused cell to avoid the transfer of mutations to the resulting embryo.

Cell Membrane Repair

Conditions of mechanical stress and pathogenic actions can lead to disruption of certain patches or formation of pores in the cell membrane. The secretory lysosomes fuse with the cell membrane at a location close to the damaged patch. This results in the release of hydrolases outside the cell. Of these hydrolases, a specialized hydrolase called acid sphingomyelinase (ASM) causes the internalization of damaged patch by the cell. Moreover, the fusion of the lysosome with the membrane provides extra lipids and prevents constriction of the cellular boundary.

 

When They Malfunction

Lysosomal malfunction leads to about 50 different types of rare inheritable metabolic disorders. New ones continue to be identified.

Defective or missing digestive enzymes lead to the accumulation of substrates within the cell, thus impairing metabolism. Such deficiency or dysfunction of lysosomal enzymes results in several inheritable metabolic disorders that are collectively termed as lysosomal storage diseases. A few major characteristics of these have been given below.

Lysosomal Storage Diseases

Lysosomal storage diseases are characterized by the presence of abnormally enlarged lysosomes containing accumulated undigested cellular components. The components or macromolecules that accumulate depends on the specific enzyme that is dysfunctional. Pompe disease, Tay-Sachs disease, mucopolysaccharidosis (MPS), and Gaucher's disease are some examples. In some cases, symptoms like short stature, bone deformities, cardiac and respiratory difficulties, enlarged head, liver and spleen, etc., are observed at birth. However, in some cases, the onset of the disease occurs at a later age and various organs are affected depending on the type of disease. The life expectancy is highly variable and those with severe forms may survive up to 5-10 years of age. These diseases are currently incurable and the treatments available mostly lessen the symptoms.

Lysosomes isolate the digestive enzymes in the cell and keep them sequestered from the other cellular parts. This "intracellular digestive system" called lysosome plays an important role in cell survival and maintaining the integrity of the cell.

 

https://biologywise.com/lysosomes-function