Agnieszka Mitrzak

Student number: 14003336

Modern concept of lysosome emerged from the effort to fractionate rat liver cells into their component organelles by homogenization and centrifugation.

It was discovered that in the ’’mitochondrial’’ fraction exist a third type of particles present that are distinct from mitochondria and

from the peroxomes.

They are called …

lysosomes.

Lysosomes – maturation. Diverse in morphological origins:

Endolysosomes.

‘Classical’ lysosomes.

Lysosomes – structure. Membrane-enclosed organelles.

Found in all eukaryotic cells.

Filled with soluble hydrolytic enzymes that digest macromolecules. ≈40 different enzymes: proteases, nucleases, glycosidases,

lipases, phospholipases, phosphatases, and sulfatases.

All are acid hydrolases. Interior pH of about 4.5-5.0.

A vacuolar H+ ATPase in the lysosome membrane pumps H+ using ATP hydrolysis as a source of energy.

Heterogeneous.

Heterogeneity of a lysosome. Diverse in shape and size. *

Diverse in acid hydrolases mediated digestive functions:

Intra- and extracellular debris breakdown.

Phagocytosed microorganisms’ destruction.

Nutrients production.

Diverse in morphological origins:

Endolysosomes.

‘Classical’ lysosomes.

Delivery pathways: Pinocytosis.

Phagocytosis.

Macropinocytosis.

Autophagy.

Pinocytosis.

Pinocytosis -a mechanism by which

extracellular fluid and its contents

are ingested.

Phagocytosis Phagocytosis begins with the neutrophil or macrophage flowing around the pathogen and engulfing it so that it winds up enclosed in a phagosome. Next lysosomes fuses with the phagosome, making a phagolysosome.

Lysosomes contain several proteases, elastase, and lysozyme.

Macropinocytosis Macropinocytosis -a highly conserved endocytic process. The extracellular fluid and its contents are ingested into cells through macropinosomes (large, heterogeneous vesicles).

Autophagy The process is important during normal cell growth, development and stresses in adaptive immune responses such as starvation and infection. Autophagy can remove:

1. Macromolecules. 2. Large protein aggregates. 3. Whole organelles.

Three different types of autophagy:

Macroautophagy Macroautophagy - a dynamic process involving

the rearrangement of subcellular membranes

to sequester cytoplasm and organelles for

delivery to the lysosome or vacuole where the sequestered cargo is degraded and recycled.

Microautophagy Microautophagy –a process involving the direct invagination of the lysosomal membrane to sequester cytoplasm.

Chaperone-mediated autophagy

Chaperone-mediated autophagy- a dynamic process involving the selective delivery of proteins

containing a specific consensus sequence

(KFERQ) to the lysosome.

Human Lysosomal Storage Diseases

Lysosomal storage diseases are due to inborn errors of metabolism which are mainly inherited in an autosomal recessive manner.

Gaucher’s disease.

Niemann-Pick disease.

The mucopolysaccharidoses.

The GM2 gangliosidoses.

Fabry’s disease.