MDH1/YKL085W Summary Help

Standard Name MDH1 1
Systematic Name YKL085W
Feature Type ORF, Verified
Description Mitochondrial malate dehydrogenase; catalyzes interconversion of malate and oxaloacetate; involved in the tricarboxylic acid (TCA) cycle; phosphorylated (2, 3 and see Summary Paragraph)
Name Description Malate DeHydrogenase 2
Chromosomal Location
ChrXI:279123 to 280127 | ORF Map | GBrowse
Gene Ontology Annotations All MDH1 GO evidence and references
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 7 genes
Classical genetics
Large-scale survey
77 total interaction(s) for 67 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 27
  • Affinity Capture-RNA: 4
  • Affinity Capture-Western: 1
  • Reconstituted Complex: 2

Genetic Interactions
  • Dosage Lethality: 1
  • Negative Genetic: 21
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 11
  • Positive Genetic: 2
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 5

Expression Summary
Length (a.a.) 334
Molecular Weight (Da) 35,650
Isoelectric Point (pI) 8.99
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXI:279123 to 280127 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1005 279123..280127 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001568

MDH1 encodes the mitochondrial isozyme of malate dehydrogenase (4) that converts malate to oxaloacetate in the tricarboxylic acid (TCA) cycle, a central hub of metabolism (2; see the TCA cycle pathway page for more details). Other malate dehydrogenase isozymes include Mdh2p, the cytosolic form involved in gluconeogenesis, and Mdh3p, the peroxisomal form involved in the glyoxylate cycle. In the aerobic utilization of glucose, pyruvate generated from glucose via glycolysis is oxidatively decarboxylated to form acetyl CoA, which is completely oxidized to carbon dioxide plus water in the TCA cycle. The TCA cycle also generates intermediates for biosynthesis of amino acids, fatty acids, heme, and for gluconeogenesis.

Mdh1p is also a component of a NADH shuttle that regulates the NAD/NADH ratio in the cytoplasm and mitochondria. The mitochondrion is impermeable to NAD and NADH, but in the malate-aspartate shuttle, Mdh1p and Aat1p convert malate to oxaloacetate and then to aspartate inside the mitochondrion, producing NADH from NAD; aspartate is transported to the cytoplasm and there converted to oxaloacetate and then to malate by Aat2p and Mdh2p, producing NAD from NADH (5). The fact that overexpressing Mdh1p extends replicative lifespan, in combination with additional genetic evidence, suggests that this shuttle pathway may play a major role in calorie restriction-mediated lifespan extension (6). Consistent with this, MDH1 expression is upregulated during calorie restriction (7).

Mdh1p is found in the mitochondrial matrix, and at least a portion exists in a large supramolecular complex in mitochondria that includes NADH dehydrogenases and other TCA cycle enzymes, which may facilitate channelling of metabolites between enzymes (4).

Last updated: 2008-09-09 Contact SGD

References cited on this page View Complete Literature Guide for MDH1
1) Thompson LM, et al.  (1988) Gene sequence and primary structure of mitochondrial malate dehydrogenase from Saccharomyces cerevisiae. Biochemistry 27(22):8393-400
2) McAlister-Henn L and Thompson LM  (1987) Isolation and expression of the gene encoding yeast mitochondrial malate dehydrogenase. J Bacteriol 169(11):5157-66
3) Reinders J, et al.  (2007) Profiling phosphoproteins of yeast mitochondria reveals a role of phosphorylation in assembly of the ATP synthase. Mol Cell Proteomics 6(11):1896-906
4) Grandier-Vazeille X, et al.  (2001) Yeast mitochondrial dehydrogenases are associated in a supramolecular complex. Biochemistry 40(33):9758-69
5) Bakker BM, et al.  (2001) Stoichiometry and compartmentation of NADH metabolism in Saccharomyces cerevisiae. FEMS Microbiol Rev 25(1):15-37
6) Easlon E, et al.  (2008) The malate-aspartate NADH shuttle components are novel metabolic longevity regulators required for calorie restriction-mediated life span extension in yeast. Genes Dev 22(7):931-44
7) Lee YL and Lee CK  (2008) Transcriptional Response According to Strength of Calorie Restriction in Saccharomyces cerevisiae. Mol Cells 26(3):299-307