Differential regulation of mitochondrial pyruvate carrier genes modulates respiratory capacity and stress tolerance in yeast.
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.
Department of Biotechnology, Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia, Valencia, Spain.
Alba
A
Timón-Gómez
Markus
M
Proft
Amparo
A
Pascual-Ahuir
D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism; D000596:Amino Acids / Q000096:biosynthesis; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism; D019069:Cell Respiration / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters; D005810:Multigene Family; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics*
D026905:Amino Acid Transport Systems; D000596:Amino Acids; D027321:Anion Transport Proteins; C403382:CRC1 protein, S cerevisiae; C573715:FMP37 protein, S cerevisiae; C573717:FMP43 protein, S cerevisiae; C573718:MPC1 protein, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; C413542:GPI13 protein, S cerevisiae; D017853:Phosphotransferases (Alcohol Group Acceptor)