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Sandrine Pouvreau"The Role of Mitochondria in skeletal muscle calcium signaling".

Abstract :


The concept that mitochondria contribute to cellular calcium homeostasis under physiological conditions is becoming the focus of an increasing research effort. On the one hand, mitochondria are equipped with an efficient machinery for calcium uptake and extrusion. They are capable of storing large amounts of calcium provided their low affinity uptake system gets exposed to local domains of high calcium generated by the opening of plasmalemmal or sarcoplasmic/endoplasmic reticulum calcium channels. On the other hand, mitochondria may modulate calcium signaling through release of several compounds that are known regulators of calcium signaling proteins: ATP and reactive oxygen species to name a few. Skeletal muscle is a tissue of choice for the study of the mitochondrial involvement in calcium signaling as it exhibits large cytosolic calcium transient as well as co-location of sarcoplasmic reticulum calcium release sites and mitochondria. However, the role of mitochondria in the regulation of subcellular calcium signalization in skeletal muscle remains a matter of debate. 

Selected publications

Paradoxical buffering of calcium by calsequestrin demonstrated for the calcium store of skeletal muscle.Royer L, Sztretye M, Manno C, Pouvreau S, Zhou J, Knollmann BC, Protasi F, Allen PD, Ríos E.J Gen Physiol. 2010 Sep;136(3):325-38. Epub 2010 Aug 16.

In vivo expression of G-protein beta1gamma2 dimer in adult mouse skeletal muscle alters L-type calcium current and excitation-contraction coupling.Weiss N, Legrand C, Pouvreau S, Bichraoui H, Allard B, Zamponi GW, De Waard M, Jacquemond V.J Physiol. 2010 Aug 1;588(Pt 15):2945-60. Epub 2010 Jun 14.

Scientific focus :

My current work focus on two mains questions: 1) how does mitochondrial calcium buffering shape cytosolic calcium levels and affect excitation-contraction coupling in skeletal muscle, and 2) how does mitochondrial reactive oxygen species production modulate intracellular calcium signaling. In this seminar, I will present recent results showing that 1) cytosolic calcium transients elicit mitochondrial calcium transients in skeletal muscle fibers. One important development of this work is the quantitative comparison of synthetic dyes and protein biosensors for the measurement of mitochondrial calcium level. 2) mitochondria exhibit a quantal production of superoxide, detected with a mitochondrial-targeted superoxide biosensor. 3) mitochondria operate as well defined units for the production of superoxide. We are currently in the process of characterizing these functional subdivisions of the mitochondrial network. 

Valentin Nagerl