%0 Journal Article
%T The long and winding road to the mitochondrial pyruvate carrier
%A John C Schell
%A Jared Rutter
%J Cancer & Metabolism
%D 2013
%I BioMed Central
%R 10.1186/2049-3002-1-6
%X An extensive body of work has accumulated over decades on the subject of mitochondrial pyruvate transport. Since the earliest proposition of a specific transporter for pyruvate in 1971 there has been continuous debate about its existence and nature [1]. Updates to techniques measuring pyruvate transport have led to revisions regarding kinetics, the metabolites that modulate transport activity, and the molecular sizes of the proposed transporter culminating in the identification of a putative transporter [2]. Unfortunately, this member of the mitochondrial carrier family (MCF) was later demonstrated to be a NAD+ transporter, whose activity resembled the pyruvate transporter in in vitro assays due an effect on the NAD+ dependent pyruvate dehydrogenase complex [3]. At the same time clinicians studying metabolic diseases were frustrated by mysterious cases of defective pyruvate metabolism, which displayed normal pyruvate dehydrogenase (PDH) enzyme activity and did not have mutations in any known components of the pyruvate metabolic system [4]. The obvious remaining candidate, the mitochondrial pyruvate carrier, could not be sequenced for mutations because the gene or genes encoding it had not been identified. In this review, we will take a historical perspective to describe the fits and starts that recently culminated in the recent identification of the long-sought mitochondrial pyruvate carrier (MPC) [5,6].Membranes provide the cell with the essential ability to delineate the unregulated external environment from the specific and homeostatically controlled internal milieu. Within the cell, compartments can be further subdivided and therefore assigned specialized functions. This separation is essential for generating and utilizing electrical potential via regulated ion current, protection of precious replicative information from mutagenic insults, enforcing colocalization of molecules, and conversion of high energy electrons into high energy phosphates using proton flow
%U http://www.cancerandmetabolism.com/content/1/1/6