Dr. Christophe Chipot
CNRS,
Nancy Université,
Vandoeuvre-les-Nancy, France

Monday, March 28, 2011
3:00 pm (CT)
3269 Beckman Institute

Abstract

Transport of the small molecules required in the metabolic cycles of the mitochondria through the internal membrane of the latter is controlled selectively by a family of integral proteins, referred to as mitochondrial carrier family or MCF. Among the members of the MCF, the ADP/ATP carrier plays a central physiological role, conveying ADP from the intermembrane space to the matrix of the mitochondria, where it will undergo phosphorylation. ATP is subsequently transported by the same protein in the opposite direction following a 1:1 stoechiometry. The topology of the electric field created by the carrier is essential for the effective and selective transport of the substrates. Increase of the ionic strength can be shown to modulate the internal electric field, thereby hampering transport. Diffusion of the nucleotides through the carrier can also be thwarted by point mutation of key residues in the protein. We will describe how the replacement of strategic amino acids alters the electric and the dynamic properties of the transporter. We will also put forth a molecular mechanism utilized by the carrier to discriminate between the substrates diffusing through it and retain only the desired ones.