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Mitochondrial transporters and disease - structure and regulation
Published on March 29, 2018 46 min
Other Talks in the Series: Mitochondria in Health and Disease
Mitochondrial transporters and disease - function and mechanism
- Dr. Edmund R.S. Kunji
- University of Cambridge, UK
Initiation and elongation of mammalian mitochondrial protein synthesis
- Dr. Linda L. Spremulli
- University of North Carolina, USA
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.
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.