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Printable Handouts
Navigable Slide Index
- Introduction
- Lecture outline
- Mitochondrial structure
- Mitochondrial functions
- Oxidative phosphorylation
- Mitochondrial DNA
- Mitochondrial DNA: function
- Heteroplasmy
- The threshold effect
- Mitochondrial DNA mutations in cancer: a history (1)
- Mitochondrial DNA mutations in cancer a history (2)
- Mitochondrial DNA mutations in cancer: NGS
- mtDNA mutations in tumours & OXPHOS function
- Trans-mitochondrial cybrids
- Trans-mitochondrial cybrids: studies
- Research example 1
- Mouse model for early-stage tumorigenesis
- PolgAmut/mutApcfl/fl mice have reduced lifespan
- PolgAmut/mutApcfl/fl mice have higher tumour burden
- PolgAmut/mutApcfl/fl tumour cells divide faster
- PolgAmut/mutApcfl/fl tumour cells are less apoptotic
- Age-related OXPHOS dysfunction summary
- What is the molecular mechanism?
- De novo serine synthesis pathway
- Confirmation of upregulated genes at the protein level
- Functional analysis of de novo serine biosynthesis
- Generation of adenoma organoids
- PolgAmut/mutApcfl/fl organoids have lower OCR
- Higher rates of de novo serine synthesis
- Resistance to serine/glycine starvation
- Serine and one-carbon metabolism
- Serine metabolism supports cancer cell growth
- SSP in normal human colonic crypts and tumours with OXPHOS dysfunction
- Immunofluorescence & OXPHOS-deficient crypts
- Metabolic remodelling in human colonic crypts
- Age-related mtDNA mutations
- Research example 2
- Manipulation of mtDNA
- DddA-derived Cytosine Base Editors (DdCBEs)
- mtDNA mutations in malignant melanoma
- Engineering of MT-ND5 in melanoma cell lines
- Mutant cells altered the immune landscape
- Mt-Nd5 mutations & immune checkpoint blockade
- Summary
- Future directions
- Acknowledgements
Topics Covered
- Mitochondrial function and mitochondrial genetics
- Mitochondrial DNA mutations in cancer
- Mitochondria and oxidative phosphorylation
- Mitochondrial DNA mutations in early stage intestinal tumorigenesis
- Mitochondrial DNA mutations in malignant melanoma
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Greaves, L. (2024, June 30). Mitochondrial DNA mutations in cancer [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 22, 2024, from https://doi.org/10.69645/XDXL1275.Export Citation (RIS)
Publication History
Financial Disclosures
- There are no commercial/financial matters to disclose.
Other Talks in the Series: Mitochondria in Health and Disease
Transcript
Please wait while the transcript is being prepared...
0:00
Hi everyone. My name is Laura
Greaves, and I work within
the Mitochondrial Research
Group which is in
the Biosciences Institute
at Newcastle University.
Today, I'm going to
talk to you about
Mitochondrial DNA
Mutations in Cancer.
0:14
Just a brief outline
of the lecture.
I'm going to start by giving
you a fairly brief overview
on mitochondrial function
and mitochondrial genetics.
Then, I'm going to
talk through some of
the research efforts of
the past which have
looked at the frequency,
the prevalence, and
the spectrum of
mitochondrial DNA mutations in
human cancers and
talk through some of
the technology used to try and
understand their
functional significance.
Then, I'm going to focus
on two more recent studies
which have taken
new approaches to
actually, try and determine
the mechanistic significance of
mitochondrial DNA
mutations of cancer.
The first is in early-stage
intestinal cancer
and the second in more
advanced malignant melanoma.
0:52
Just to start off
with a little bit
about mitochondrial structure.
So, mitochondria are
essential intracellular
organelles, which are present in
most eukaryotic cells, and they
perform a number of crucial
cellular functions.
Structurally they're double
membrane organelles.
The outer membrane is completely
surrounds the mitochondria and
the inner membrane which
encapsulates the
mitochondrial matrix.
The inner membrane is highly
folded and this leads
to the formation of
structures known as cristae.
It's on these cristae
where the process
of oxidative
phosphorylation occurs.
Mitochondria are actually not
these general
bean-shaped entities,
but they are dynamic organelles
which are constantly fusing
and dividing and
they actually form
a reticular network
within the cell.
1:34
Mitochondria are known as
the powerhouses of the cell
and this is because
they have a key role in
the production of ATP through
oxidative phosphorylation (OXPHOS).
However, alongside
that major role,
they have a role in apoptosis,
cell signaling, cell growth,
and differentiation.
So, they have a major effect on
the overall function
of the cell.