Figure 220

Pathways of delivery of materials for digestion in lysosomes. Most of the material to be digested comes from endocytotic pathways (red arrows). It consists of small extracellular particles that are internalized by both endocytosis and receptor-mediated endocytosis. Large extracellular particles such as bacteria and cellular debris are delivered to lysosomes via the phagocytotic pathway (blue arrows). The cell also uses lysosomes to digest its own proteins and other intracellular particles via the autophagic pathway (green arrows). Intracellular particles are isolated from the cytoplasmic matrix by the membranes of the endoplasmic reticulum, transported to lysosomes, and subsequently degraded.

Cytoplasmic proteins and organelles are also substrates for lysosomal degradation in the process of autophagy

A number of cytosolic proteins, organelles, and other cellular structures can be degraded in the lysosomes (Fig. 2.21). Generally, this process can be divided into three well-characterized pathways:

• Macroautopbagy is a nonspecific process in which a portion of the cytoplasm or an entire organelle is surrounded by an intracellular membrane of endoplasmic reticulum to form a vacuole called an autophagosome. After fusion with a lysosome (autopbagolysosome), the contents of the vacuole are degraded in a manner similar to that occurring within the phagolysosome. Macroautopbagy occurs in the liver during the first stages of starvation (Fig. 2.22).

• Microautopbagy is also a nonspecific process in which cytoplasmic proteins are degraded in a slow, continuous process under normal physiologic conditions. In mi-

croautophagy, small cytoplasmic soluble proteins are internalized into the lysosomes by invagination of the lysosomal membrane.

Chaperone-mediated direct transport to lysosomes is the only selective process of protein degradation and requires assistance from a specific chaperone protein called hsc73. This process is activated during nutrient deprivation and requires the presence of targeting signals on the degraded proteins and a specific receptor on the lysosomal membrane. Chaperone-mediated direct transport resembles the process of protein import to various other cellular organelles: hsc73 binds to the protein endoplasmic reticulum endoplasmic reticulum

autophagosome vacuole

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