Mitochondria and Cell Death
If Ca+ is so important for a cell, but it is also dangerous. How do we ensure that there is enough
available, but can be readily accessible, but not so much that it’s lethal to the cell?
How calcium gets in the cell, in the different storage organelles and how it gets out
Use knowledge on membrane fluidity, membrane transport, concentration gradients, binding
proteins (those that specialize in binding Ca+, not included in the intracellular free-Ca+
concentration, but still readily available)—how do we replenish the Ca+ reserves and ensure
there isn’t too much.
Signal transduction—can build on them with Ca+
What happens to cells when they are not healthy? They need to die at some time, but why?
-Certain mutations (are preferable to kill cells)
-The cells are no longer needed—pruning (often used for neurons, but other cell types as well)
-prevents the ailing of neighbouring cells.
-to control the number of cells, cell mass
-Cell turnaround (skin cells, RBCs, WBCs)
-Damage, stress, anything that affects a good life of a life
Positive reasons for killing cells?
-During development, organs and changes of structure need to change, must eliminate some
cells, so the organism can change. It’s a developmental necessity. (i.e. tadpoles to lose their
There are many different reasons why cells need to die and many different ways how it will
Many sub-groups and sub-divisions of cell-death, but will study:
-Necrosis and apoptosis (the basics)
Total number of cells, total cell mass—the controlled forced—if not controlled, it’ll never stop
growing and they will not receive enough nutrients for sustaining a healthy life. They are
programmed for a healthy life until the time is up (to maintain). Cell cycle regulation will
review these concepts.
Introduction to signal transduction was in today’s topic
-signaling molecules and messengers
-receptors and relaying information into cells (signal transduction)
One cellular response is death
-regardless of the reason, we will focus on what happens than the reasons they communicate
Which of the following does not occur in necrosis?
B- Blebbing C- Lysis
D- Lysosomal membrane degradation: hallmark of necrosis
Necrosis vs. apoptosis—differences on the slides and blackboard
However, what is lysis? To break apart—the membrane ruptures and the cell releases its
contents in the extracellular space—this is bad for the cell and is messy for the neighbouring
Blebbing: Blistering—the membrane loses contact with the neighbouring cells and begins to
form these blebs (not observed in necrosis)
Lysosomal membrane degradation:
Cell Death: Necrosis vs. Apoptosis
Necrosis: Normal Cell Swelling (reversible irreversible) Disintegration
- Why might it swell? Its expanding and can make a bigger mess, more room before and
when explode, everything is further back
-hypertonicity, water coming in—is there something going on in the membrane?
-changes in the cell is making the membrane more fluid and the membrane is less able to be
more selective with permeable; the cell is swelling. What can prevent it (from membrane
dynamics)? Rearranging the phospholipids, changing the cholesterol ratio. At this point, it is
still reversible and the cell can change it—but if it’s not done quickly, then it’ll become
irreversible swelling and it will die—because the membrane rupture, contents are
everywhere and there is disintegration. It will also affect neighbouring cells.
Apoptosis, on the other hand is: a well planned, methodical process—nice and neat and well
planned. It’s nice and neat and well planned. The cell will condense, change shape, cytoskeleton
shring, nucleolus dissolves, DNA fragments, everything goes into vesicles known as “apoptotic
bodies” and the neighboring cells will phagocytose the apoptotic bodies and there will be no
Normal Cell Condensation Fragmentation Apoptotic bodies
-we will see the cell condense and change shapes
-the DNA becomes fragmented, and everything goes into membranes known as apoptotic
bodies, which are vesicles and there will be no “mess” –or collateral damage
-how the cell will die is way different.
Necrosis is more of a consequence of something and apoptosis can be a consequence or a
planned event. We can sometimes tell when a cell will apoptose Necrosis: the most accepted model for necrosis (consequential, but not clear-cut)—most
The calpain-Cathepsin pathway:
-Insults or damages of the cell
-Changes in the membrane (fluidity, membrane potential, permeability, not in an optimal
manner—homeostasis is being disrupted)
-Things are not functioning in a good matter
-i.e. Ca+ channels letting too much Ca+ into the cell
-calcium has 2 organs where its being stored
-Ca+ stores are beginning to release the Ca+ that they have stored
-2 means to increase the Ca+ in the cell—it is no longer a friend--in this case, it’ll reach a certain
concentration and activate calpain (an enzyme, a protease)—it’s job is to digest protein and it’s
favourite is to digest the content in the lysosomal protein —the digestion enzymes (inside the
lysosome)—often in the lysosome, due to the low pH. What happens when found in the
cytoplasm? In a healthy cell, the pH is around 7, those who prefer a lower one would be more
neutralized and less efficient. The membrane isn’t functioning optimally. Since the cell is no
longer healthy, the Cathepsin is not a fan of the acidic pH, and in the lysosome, it isn’t the most
favoured enzyme, but since the lysosome has ruptured, and it’s in a less acidic place, it has
picked up its activity and becomes a star, it’s also a protease—its target=all the cellular content:
cytoskeleton, proteins in organelles, globular proteins soluble in cytoplasm—many things to
start digesting. The cell slowly disintegrates into the cell’s death. It’s all calcium’s fault.
The swelling comes before all this: the swelling comes from the membrane not able to retain
permeability and fluidity; channels open that shouldn’t be, ions through phospholipids that
shouldn’t be there—letting ions and water into the cell—swelling leads to a rise in the calcium.
Lysosome bursting now vs. other times?
-other times: if it ruptures, lots of cellular damage, however, may not have a huge
concentration of calcium, which means the rest of cell (with membrane) is healthy enough to
contain, however, it may still rupture and die.
Could be a similar reason why the cell wants to die
Way its achieved is different in apoptosis
-cytoplasm shrinks, chromatin condenses, the nuclear envelope begins to dissolve, the DNA is
broken up into smaller portions (DNA laddering), blebbing-the cell will lose its ability to adhered
to neighbouring cells and it’s environment and a membrane will form these blebs and
eventually the cell will be broken up into vesicles that contains parts of the cell body, that will
be sent to neighbouring cells to be phagocytosis. What features do apoptotic bodies have that promote autophagy?
When autophagy occurs, it is needed to maintain homoeostasis. Phosphatidylserine is needed
to go to the outer membrane, and the proteins are needed to recognise the apoptotic bodies to