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Printable Handouts
Navigable Slide Index
- Introduction
- Atomic structures of yeast ADP/ATP carriers
- Architecture of the yeast ADP/ATP carrier
- Glutamine braces and matrix salt bridge network
- Cytoplasmic salt bridge network is not interacting
- Thermostability assays with CPM
- Inhibitors of the mitochondrial ADP/ATP carrier
- CPM targets two cysteines of the ADP/ATP carrier
- BKA: Raised baseline and temperature shift
- Mutagenesis modulates interaction energy
- Thermostability of the matrix state
- Features of the inter-domain interfaces
- Proposed domain motions for formation of network
- Mitochondrial disease & dysfunctional transporters
- Salt bridges and substrate binding site in disease
- Role of the human aspartate/glutamate carrier
- The aspartate/glutamate carrier is a chimera
- Architecture of the regulatory domain 1
- Architecture of the regulatory domain 2
- Proposed mechanism for calcium-regulation
- Mutations that lead to citrin deficiency
- The mitochondrial ATP-Mg/Pi carrier
- The regulatory domain of ATP-Mg/Pi carrier
- Calcium regulation of ATP-Mg/Pi carrier (1)
- Calcium regulation of ATP-Mg/Pi carrier (2)
- Conclusions
- Thank you
Topics Covered
- The involvement of salt bridge networks in the transport mechanism
- Conformational changes in transport
- Involvement of mitochondrial carriers in human diseases
- Calcium regulation of transport
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Talk Citation
Kunji, E.R. (2018, March 29). Mitochondrial transporters and disease - structure and regulation [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 8, 2024, from https://doi.org/10.69645/DXSR6693.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Edmund R.S. Kunji has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Mitochondrial transporters and disease - structure and regulation
Published on March 29, 2018
46 min
Other Talks in the Series: Mitochondria in Health and Disease
Transcript
Please wait while the transcript is being prepared...
0:00
Welcome to my second talk on "Mitochondrial Transporters and Disease".
My name is Edmund Kunji.
I work for the Medical Research Council
Mitochondrial Biology Unit of the University of Cambridge.
Our work is aimed to understand the role of
"Mitochondrial Transport in Human Physiology and Disease".
In this second talk,
I will discuss the structural mechanism of mitochondrial carriers which are
the main transporters involved to the imports and
exports of compounds in and out of mitochondria.
0:36
To understand the structural mechanism better,
my lab solve the atomic structures of
two yeast mitochondria ADP/ATP carriers called Aac2 and Aac3,
which allowed us to compare these structures to the bovine ADP/ATP carrier,
which we had already a structure shown in the first lecture.
Aac2 from yeast is the transporter involved in ADP/ ATP transports under conditions of
aerobic growth while Aac3 is the transporter
involved in ADP/ ATP exchange under conditions of anaerobic growth.
When we solved the structure it was clear that these molecules are very very
similar and we also know by functional work that they carry out the same role.
So, on the mechanistic level,
they are in fact identical.
The reason that yeast has two different transporters is to regulate
the expression levels of these transporters under different conditions.
Under aerobic conditions,
you need a lot of ADP/ATP carrier, therefore Aac2 is expressed. Under anaerobic conditions,
you want to repress the amount of ADP/ATP carriers,
and just maintain enough to stabilize
the mitochondria by allowing ATP being imported from the cytosol
to use for the maintenance of the mitochondrion.
Let's review again the basic structure of mitochondrial carriers and this
time we will look at
the yeast ADP/ATP carriers and compare them to the bovine one from the first lecture.