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Printable Handouts
Navigable Slide Index
- Introduction
- Apoptosis
- Apoptosis - what is it good for?
- How does a cell kill itself?
- Caspase proteases are required for apoptosis
- Two types of apoptotic caspases exist
- Pathways to caspase activation
- Mitochondrial/intrinsic pathway of apoptosis
- Point of no return!
- MOMP commits cells to die
- Genetic evidence for this pathway
- MOMP is rapid and often complete
- MOMP is typically the point of no return
- MOMP need not be all or nothing
- MOMP has non-lethal signalling functions
- Summary (1)
- What regulates mitochondrial permeabilisation?
- BCL-2 family regulate mitochondrial permeabilisation
- Pro-apoptotic BAK and BAX induce MOMP
- Pro- and anti-apoptotic BCL-2 proteins dictate MOMP
- BAX and BAK are typically essential for MOMP
- BOK can also induce MOMP in some settings
- Blocking mitochondrial apoptosis affects development
- BAK/BAX localisation
- BAX and BAK oligomerize to form lipid pores
- Summary (2)
- Can we target mitochondrial apoptosis in disease?
- Cell death prevents and treats cancer
- Anti-apoptotic BCL-2 proteins promote cell survival
- BH3-mimetics
- Targeting BCL-2 to treat cancer works
- Can we target mitochondrial apoptosis in other ways?
- MOMP is a point of no return
- TNF is up-regulated following MOMP
- MOMP is pro-inflammatory, caspases silence this
- MOMP engages inflammation, caspases silence this
- How do mitochondria drive inflammation?
- MOMP is inherently pro-inflammatory
- Mitochondrial inner membrane permeabilisation
- Is it better to kill cancer cells via CICD?
- CICD effectively treats cancer
- Summary (3)
- Acknowledgements
- Contributors
Topics Covered
- Apoptosis
- Caspase activation and function in apoptosis
- Mitochondrial/intrinsic pathway of apoptosis
- Mitochondrial outer membrane permeabilisation (MOMP)
- BCL-2 family proteins role in mitochondrial permeabilisation
- Targeting mitochondrial apoptosis in disease
- Caspase-independent cell death
Talk Citation
Tait, S. (2021, October 31). Mitochondria and apoptosis [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 23, 2024, from https://doi.org/10.69645/AIER4051.Export Citation (RIS)
Publication History
Financial Disclosures
- There are no commercial/financial matters to disclose.
A selection of talks on Cancer
Transcript
Please wait while the transcript is being prepared...
0:00
Good afternoon everyone.
My name is Stephen Tait.
I'm a professor of mitochondrial cancer biology based at
the University of Glasgow and the Cancer Research UK Beatson Institute.
Today I'm going to be giving a lecture on
mitochondria and the role of mitochondria in apoptosis.
0:22
What is apoptosis?
You'll see in this movie here,
these are HeLa cells,
so a cervical cancer cell line that's been treated with two prototypic chemotherapies,
called TRAIL and ABT-737.
At the start of the movie, the cells receive this signal.
They are viable, they're spread out,
and they are stuck onto the substrate.
In this case, a plastic dish in which they're growing,
and upon receipt of these signals,
that cells rapidly undergo what we call apoptosis,
a form of cell suicide,
a regulated form of cell death.
You can see very quickly as the cells undergo cell death,
they shrink, and they form what we call membrane blab.
They almost looked like pieces of popcorn, I always think.
Then, ultimately, they detach from whatever they've been stuck down to.
You can see quite nicely the end,
that's the cells undergoing cell death,
they shrink, and then they detach from the plate.
Apoptosis is a regulated form of cell death;
it occurs in billions of cells each day in a body.
1:25
Apoptosis, what is it good for?
Which roles does it have in our body?
One of the key processes apoptosis is involved in
is actually preventing cancer and it's used to treat cancer.
What do I mean by this?
Cells that are triggered to undergo apoptosis may be damaged,
their DNA is damaged and
that can send a signal to the cell to go
and kill itself through the process of apoptosis.
In doing so, that prevents cells that have mutations from becoming cancerous.
Equally, we use apoptosis a lot in the clinic.
Most anticancer therapies when they do work,
they work by killing cells and often they kill cancer cells through the process of apoptosis.
Apoptosis is really important in the prevention and treatment of cancer.
Secondly, I've highlighted here,
it's really important in immunity.
As our immune systems develop,
generally cells or immune cells do react self-antigen itself presented peptides.
These cells are eliminated through the process of apoptosis.
In doing so, as their immune systems develop,
we then fail to develop an auto-immune response,
which is important of course,
because we don't want autoimmunity.
A second component or at least one of many components in immunity is
that apoptosis is often the form of cell death that's triggered
by cytotoxic T-cells as they encounter either
infected or potentially cancerous cells in our body,
cytotoxic T-cells will trigger apoptotic cell death in virally infected cells.
Then another processes them and highlighted here is
the apoptosis which is very important in development.
We'll come back to this point later in the talk.
As we undergo embryonic development,
as our organs and our features form during embryogenesis,
many cells undergo apoptosis and allow the sculpting of
different organs and during this or because of this we then develop properly.
These are just three processes I've highlighted here.
I just want to state at the end,
it's also involved in many other processes that keep us healthy as we develop,
as we undergo aging as well.
Apoptosis is a really important process.