Learning from Yeast about Mitochondrial Carriers

Abstract

Mitochondria are organelles that play an important role in both energetic and synthetic metabolism of eukaryotic cells. The flow of metabolites between the cytosol and mitochondrial matrix is controlled by a set of highly selective carrier proteins localised in the inner mitochondrial membrane. As defects in the transport of these molecules may affect cell metabolism, mutations in genes encoding for mitochondrial carriers are involved in numerous human diseases. Yeast Saccharomyces cerevisiae is a traditional model organism with unprecedented impact on our understanding of many fundamental processes in eukaryotic cells. As such, the yeast is also exceptionally well suited for investigation of mitochondrial carriers. This article reviews the advantages of using yeast to study mitochondrial carriers with the focus on addressing the involvement of these carriers in human diseases.

Enhanced glycerol assimilation and lipid production in Rhodotorula toruloides CBS14 upon addition of hemicellulose primarily correlates with early transcription of energy-metabolism-related genes

“…This includes genes encoding enzymes involved in the tricarboxylic acid (TCA) cycle, such as NADP + -specific isocitrate dehydrogenase (ICDH), succinate-CoA ligase, and fumarate hydratase (RHOT145845, -7009 and -5604, respectively), or in the synthesis of cofactors of mitochondrial enzymes, such as riboflavin (RHOT149252, 2556 and 2045), lipoic acid (by lipoyl synthase, RHOT145711) and thiamine pyrophosphate (TPP, by thiamine pyrophosphokinase, RHOT149040). Lipoic acid and TPP are cofactors of pyruvate dehydrogenase and α-keto glutarate dehydrogenase [41].…”

Heterologous (Over) Expression of Human SoLute Carrier (SLC) in Yeast: A Well-Recognized Tool for Human Transporter Function/Structure Studies

“…Even the yield per cell of the expressed protein remained the same as wt yeast and the TM6* strain produced about 2–3 times more biomass, thus increasing the amount of the target protein [ 147 ]. One of the areas in which S. cerevisiae has proven to be an especially fruitful model is the area of mitochondrial research [ 154 ]. Indeed, the high similarity between yeast and human mitochondrial biogenesis and function renders S. cerevisiae an excellent model for studying human mitochondrial physiopathology [ 154 , 155 , 156 , 157 ].…”

“…One of the areas in which S. cerevisiae has proven to be an especially fruitful model is the area of mitochondrial research [ 154 ]. Indeed, the high similarity between yeast and human mitochondrial biogenesis and function renders S. cerevisiae an excellent model for studying human mitochondrial physiopathology [ 154 , 155 , 156 , 157 ]. Systematic approaches have been performed to optimize S. cerevisiae for recombinant membrane protein production, with the specific goal of understanding the molecular barriers to achieve high yields [ 158 ].…”

Ctp1 and Yhm2: Two Mitochondrial Citrate Transporters to Support Metabolic Flexibility of Saccharomyces cerevisiae

“…Therefore, this metabolic flexibility found in yeast depends on the specific substrates available during growth conditions. In this respect, mitochondrial carrier proteins play a key role because they transport a variety of substrates across the inner membrane of the organelles, thus connecting mitochondria with cytosolic reactions [10][11][12]. Among other 2 of 15 substrates, citrate is a key metabolic intermediate involved in several pathways and, therefore, the flux of this molecule between different cellular compartments is strictly regulated.…”