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  UPCOMING EVENTS   Selected Seminar        
Date: 20 October 2017
Time: 11:00am | Level 3, IMCB Seminar Room 3-46, Proteos
Speaker: Dr. Thomas Simmen
Title: Redox and tethers determine Ca2+ signaling at the mitochondria-associated membrane (MAM)

Tumor cell metabolism is frequently aberrant and shifts its energy generation away from mitochondria towards glycolysis. Currently, few molecular mechanisms are known that can lead to such a metabolic shift. Research from several labs, including ours, have identified calcium-mediated crosstalk at the mitochondria-associated membrane (MAM) as such a mechanism. The MAM is formed by close apposition between the endoplasmic reticulum (ER) and mitochondria, where the two organelles exchange calcium ions. This flux is a determinant of mitochondria metabolism, and depends on the following factors: i. The extent of ER-mitochondria apposition, ii. The extent of mitochondrial calcium release and uptake. iii. The extent of ER calcium release and uptake. Our lab studies proteins that control this latter factor. We have identified ER chaperones and oxidoreductases as critical regulator of ER-mitochondria calcium flux. These proteins exert their functions as regulators of ER calcium channels and pumps. The presentation will focus on the latest results on calnexin, an activator of SERCA pumps. We show that calnexin determines mitochondria metabolism through this function, as an opposing mechanism to the previously identified inhibition of SERCA by TMX1. Moreover, calnexin and TMX1 aberrant expression patterns in cancer, consistent with their molecular functions.

After growing up in the mountain town of Chur in Switzerland, I graduated with a PhD in the laboratory of Dr. Walter Hunziker in Lausanne/Switzerland. During this early time, my work focused on the sorting of proteins to the bnsoalteral surface of polarized cells, culminating with the description of the AP-4 sorting complex in this mechanism. I completed my studies with postdoctoral studies in the laboratories of Dr. Roberto Sitia in Milan/Italy and Dr. Gary Thomas in Portland OR/USA, where I shifted my interests to the redox control of the endoplasmic reticulum (ER) and to the interaction of the ER with mitochondria. Upon starting my own laboratory at the University of Alberta in 2005, I focused on this latter topic. We discovered a series of ER-mitochondria contact site markers, including the chaperones and oxidoreductases calnexin and TMX1. We also described sorting mechanisms for this membrane domain with the identification of cytosolic sorting factors, such as Rab32 and PACS-2, as well as protein lipid modifications (palmitoylation). Our latest research focuses on understanding the significance of our findings for human disease, including cancer and neuroinflammation.

Host: Prof. Walter Hunziker

Seminar is open to public, registration is not required.


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