BIOC 201 - Discussion Session #2: Topic 1 (Lysosomes)

September 17, 2014

Malvika Govil
Lysosomes are membrane-bound organelles found in the cytoplasm
of animal and plant cells. They have specialized structural features
and contents that enable them to perform their main function: the
degradation and recycling of undesirable material or damaged
components found either outside the cell or within the cell. Material
in the extracellular fluid undergoes endocytosis by the plasma
membrane, forming transport vesicles that merge with endosomes,
which are membrane-bounded compartments in eukaryotic cells.
These can either merge with lysosomes or gradually mature to form
lysosomes themselves. Molecules can also bind directly to the
lysosome membrane, usually through surface receptors, which are
taken into the organelle along with the binding molecules. This
ensures specificity of breakdown and also limits the signaling and
intake of molecules for degradation, since not as many receptors
remain exposed to the cytosol.
Lysosomes contain more than 50 hydrolytic enzymes, known as
hydrolases, which break down macromolecules such as proteins,
carbohydrates, lipids and nucleic acids. These enzymes have an
optimal acidic pH of about 5.5, which is maintained in the lysosome
by proton pumps that bring in H+ ions and chloride ion channels
that pump Cl- ions out. The membrane of the lysosome protects the
slightly basic cytosol (around pH7.4) and its contents from the acidic
environment. Since the hydrolases are inactive at the cytosols
alkaline pH, their leakage into the cytosol does not lead to the
digestion of molecules or organelles. Additionally, as mentioned in
the discussion, the lysosome is prevented from digesting its own
proteins because their specialized 3D structures protect the bonds
that maintain their shape and function.
Autophagy is essentially the gradual turnover by lysosomes of
molecules and organelles that are found in the cell; in this case the
cell components are usually damaged, but autophagy is also
stimulated by starvation. Initially, a targeted substance in the
cytosol is surrounded by a membrane, forming a vesicle that is also
known as an autophagosome. The lysosome engulfs it,
internalizing and then hydrolyzing the contents into their smaller
components, which are usually released into the cytosol and
recycled in various reactions. For example, properly formed
macromolecules are made to replace the damaged ones that were
degraded by the lysosome. Interestingly, starvation can stimulate
more selective autophagy; specific proteins are targeted to the
lysosome and HSP70 family chaperones unfold the polypeptide
chains to allow their transport across the membrane. This can help
target proteins that are nonessential to survival, and use recycled
amino acids and energy released to power necessary metabolic
processes or synthesize essential proteins. Autophagy is also
important in the regulation of the amount of secretory molecules

and vesicles available for export by the cell, since it contributes to

their breakdown.
The degradation process can be harmful to humans if certain kinds
of viruses, for which the conditions inside the lysosome are
favorable for replication, invade the cells, since the spread of the
virus would be enhanced. Lysosomes are important in degrading
protein aggregates, dysfunctional organelles, and other faulty
substances in the cell through autophagy, which prevents diseases
as well as ageing processes. In one study that was brought up, livers
in older rats usually did not function as well as in in younger rats,
but by inducing the overexpression of receptors on lysosomes
membranes in the livers of old rats, the livers in both groups of rats
performed equally well. This demonstrated the anti-ageing effects of
degradation of intercellular material by lysosomes.
The best analogy in our group likened lysosomes to vultures circling
in the desert, picking out weak, dead animals (i.e. undesirable or
faulty substances), which they consumed and digested, thus
recycling energy and useful materials in the ecosystem.
Some questions we had after discussion:
- How does the endomembrane system identify dysfunctional
organelles or faulty molecules to enclose and transport to the
lysosome does ubiquitin play a role in this process?
- What is it about the 3D structures of lysosomes proteins that
prevents their digestion by the hydrolases?
- Why cant lysosomes digest prions or viruses that enter the
cell and proliferate or cause damage?