Differential Regulation of Mitochondrial Pyruvate Carrier Genes Modulates Respiratory Capacity and Stress Tolerance in Yeast

Alba Timón-Gómez,Markus Proft,Amparo Pascual-Ahuir,Nai Sum Wong

doi:10.1371/journal.pone.0079405

Abstract

Mpc proteins are highly conserved from yeast to humans and are necessary for the uptake of pyruvate at the inner mitochondrial membrane, which is used for leucine and valine biosynthesis and as a fuel for respiration. Our analysis of the yeast MPC gene family suggests that amino acid biosynthesis, respiration rate and oxidative stress tolerance are regulated by changes in the Mpc protein composition of the mitochondria. Mpc2 and Mpc3 are highly similar but functionally different: Mpc2 is most abundant under fermentative non stress conditions and important for amino acid biosynthesis, while Mpc3 is the most abundant family member upon salt stress or when high respiration rates are required. Accordingly, expression of the MPC3 gene is highly activated upon NaCl stress or during the transition from fermentation to respiration, both types of regulation depend on the Hog1 MAP kinase. Overexpression experiments show that gain of Mpc2 function leads to a severe respiration defect and ROS accumulation, while Mpc3 stimulates respiration and enhances tolerance to oxidative stress. Our results identify the regulated mitochondrial pyruvate uptake as an important determinant of respiration rate and stress resistance.

Highlights

Mitochondria have many essential functions in eukaryotic cells
In conditions where the oxidation of pyruvate via the tricarboxylic acid cycle (TCA) and the mitochondrial electron transport chain is greatly repressed, the dominant mitochondrial import system for pyruvate is composed of Mpc1 and Mpc2 (Figure 1 and [11,12])
This is the case for yeast cells in an environment in the presence of fermentable carbohydrates when most of the mitochondrial pyruvate is dedicated to biosynthetic processes such as the synthesis of amino acids

Summary

Introduction

The generation of ATP by oxidative phosphorylation is their primary function, mitochondria play important roles in signal transduction, conversion of metabolites and the biosynthesis of organic compounds. When glucose becomes limiting for example during the diauxic shift, a major transcriptional program is initiated to activate the catabolism of non fermentable carbon sources and oxidative metabolism at the mitochondria [4]. This adaptive process is regulated by conserved signal transduction such as positively by the Snf signaling pathway or negatively by protein kinase A [5,6]. Yeast cells growing on non fermentable substrates show a largely enhanced mitochondrial biomass and respiratory capacity

Methods

Results

Conclusion