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Printable Handouts
Navigable Slide Index
- Introduction
- The Lab (goals)
- Complexity of the mitochondrial network
- Oxidative phosphorylation
- Calcium signaling: driving activity
- The calcium–mitochondria dialogue
- Pathways of the mitochondria
- Mitochondrial responses to calcium in living cells
- Mitochondrial calcium uptake shows a threshold
- Mitochondria make close contact with ER
- Mitochondria are colocalised with ER
- Calcium oscillations
- The transfer of calcium to the mitochondria
- Mitochondrial calcium uptake
- The functional importance of MICU1
- Calcium uptake is quicker in MICU1 patients
- Cytosolic calcium is lower in MICU1 patients
- Increased resting mitochondrial calcium content
- MICU1 controls mitochondrial calcium uniporter
- A working hypothesis
- Inhibition of calcium export
- Importance of a threshold calcium concentration
- Knockout of the mitochondrial calcium uniporter
- The relationship is a dialogue, it is reciprocal
- Cytosolic calcium wave in astrocytes
- Cytosolic calcium wave after depolarisation
- Spatial calcium buffering
- Mitochondrial calcium uptake shapes signaling
- Mitochondrial permeability transition pore (mPTP)
- Calcium retention capacity and PTP opening
- The PTP represents a potential therapeutic target
- PTP opening causes loss of membrane potential
- PTP opening causes mitochondrial swelling
- Mitochondrial calcium 'overload' causes cell death
- Limiting mitochondrial calcium ‘overload’
- Inhibiting mPTP opening reduces infarct size
- Cyclophilin D knockout mice: reduced infarct size
- Preconditioning confers protection to heart
- Imaging PTP opening and calcium (1)
- Imaging PTP opening and calcium (2)
- Candidate molecules for identity of the mPTP
- mPTP opening is of major importance in the heart
- Why do cells die?
- Cell death triggers
- Conclusion
Topics Covered
- Calcium signalling, ubiquitous and associated with increased energy demand
- Mitochondria machinery to for taking up calcium from the cytosol
- The transfer of calcium from cytosol to mitochondria (stimulation of oxidative phosphorylation & matching energy supply with demand)
- Mutations in proteins that regulate mitochondrial calcium uptake (causation of a neuromuscular disease, possibly by mitochondrial calcium overload)
- Acute severe calcium overload causes cell death during reperfusion of ischaemic tissues
- The permeability transition pore, a potential therapeutic target
Links
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Talk Citation
Duchen, M.R. (2018, February 28). Mitochondria and calcium signaling in cell life and cell death [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 21, 2024, from https://doi.org/10.69645/DCIB4601.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Michael R. Duchen has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Other Talks in the Series: Mitochondria in Health and Disease
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Michael Duchen,
and I work in University College London.
I'm going to talk about the relationship between
cellular calcium signaling and mitochondrial function in health and
disease in a talk I've entitled
"Mitochondria and Calcium Signaling in Cell Life and Cell Death".
0:15
So, the over-arching goal of the work in my lab is to
illuminate the roles of mitochondria in health and disease.
We want to understand the place of mitochondria in
cell physiology and in pathophysiology.
We want to answer questions about
how mitochondria influence and how they influenced by changes in cell function.
We want to understand the processes and
pathways that lead to mitochondrial damage in disease.
We want to understand how much mitochondrial dysfunction
has an impact on cell physiology.
Ultimately, we're really interested in identifying
potential mitochondrial pathways that we can
target as therapeutic targets in human disease.
0:52
With these images, I want to emphasize the complexity and
the dynamic nature of the mitochondrial network in cells,
far removed from the bean-shaped static structures,
which are illustrated in most biochemistry textbooks.
The central image shows a living astrocytes in which
we've labelled the mitochondria with a fluorescent dye.
And we've imaged the cell on the stage of the confocal microscope.
And I hope you can see how the mitochondria form a
wonderful filigree network that ramifies throughout the cell.
The movies emphasize the dynamic nature and responsiveness of mitochondria.
The movie playing on the left of your screen shows mitochondria expressing
a fluorescent protein and imaged in the peripheral nerve of
a living mouse by my colleague Marija Sajic.
You can see how the mitochondria constantly on the move,
trafficking towards nerve terminal where they needed to provide the energy required for,
transductions that take place at the nerve terminal,
or back towards the cell body in the spinal cord.
The image on the right shows live imaging of a HeLa cell,
which is expressing a mitochondrial targeted green fluorescent protein,
and you can see how the mitochondria constantly moving,
sensing their local environment,
fusing together, splitting apart.
These are dynamic reactive structures,
highly engaged with the business of cell physiology.