AAC3/YBR085W Summary Help

Standard Name AAC3 1
Systematic Name YBR085W
Alias ANC3
Feature Type ORF, Verified
Description Mitochondrial inner membrane ADP/ATP translocator; exchanges cytosolic ADP for mitochondrially synthesized ATP; expressed under anaerobic conditions; similar to Aac1p; has roles in maintenance of viability and in respiration; AAC3 has a paralog, PET9, that arose from the whole genome duplication (1, 2, 3 and see Summary Paragraph)
Name Description ADP/ATP Carrier 1
Chromosomal Location
ChrII:415983 to 416906 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All AAC3 GO evidence and references
  View Computational GO annotations for AAC3
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 6 genes
Resources
Classical genetics
null
overexpression
Large-scale survey
null
overexpression
unspecified
Resources
28 total interaction(s) for 25 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 18
  • Affinity Capture-RNA: 1
  • PCA: 2

Genetic Interactions
  • Dosage Rescue: 1
  • Negative Genetic: 2
  • Phenotypic Suppression: 1
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 307
Molecular Weight (Da) 33,313
Isoelectric Point (pI) 10.62
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrII:415983 to 416906 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1997-01-28
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..924 415983..416906 2011-02-03 1997-01-28
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000000289
SUMMARY PARAGRAPH for AAC3

PET9, AAC1, and AAC3 are members of a gene family encoding adenine nucleotide translocators of the mitochondrial inner membrane (4, 1). The primary role of the translocators is to pump ADP into the mitochondrion and ATP out of the organelle. However, under certain conditions, such as during exponential growth on glucose under aerobic conditions, they act in the opposite direction, importing ATP into mitochondria (5). Competition experiments suggest that they also import heme into mitochondria, and all three proteins bind to heme (6). Genetic evidence indicates a possible role of the ADP/ATP carriers in apoptosis (7). Pet9p physically interacts with various complexes of the mitochondrial inner membrane, including the TIM23 complex and the cytochrome c oxidase - ubiquinol-cytochrome c reductase supercomplex, and these interactions are dependent on the presence of the phospholipid cardiolipin (8, 9).

PET9 encodes the major isoform of the translocator (10). A pet9 null mutant strain, despite having wild-type copies of AAC1 and AAC3, is unable to respire (i.e., cannot utilize non-fermentable carbon sources such as glycerol or ethanol), and additionally displays a "petite-negative" phenotype, meaning that it cannot survive the loss of the mitochondrial genome (11). AAC1 is expressed at a very low level compared to PET9, and can complement the pet9 mutant phenotypes only if the gene, with its native promoter, is present in multiple copies (4). AAC3 is expressed primarily under anaerobic conditions, and is also capable of complementing the pet9 mutant phenotypes if overexpressed (1). The pet9 aac1 aac3 triple null mutant is viable under standard conditions (growing on fermentable carbon sources such as glucose), but is inviable under anaerobic conditions (12).

All three paralogs are similar to adenine nucleotide translocators in higher organisms. Mutations in the human ANT1 gene (OMIM), encoding the heart and skeletal muscle-specific isoform, are associated with serious diseases. Dominant missense ANT1 mutations are found in patients with progressive external ophthalmoplegia. The equivalent mutations in S. cerevisiae PET9 cause reduction or loss of function, and may lead to the formation of an unregulated channel in the mitochondrial membrane (13, 14). A recessive ANT1 mutation, whose yeast equivalent in PET9 causes a complete loss of function, is associated with hypertrophic cardiomyopathy (15).

Last updated: 2010-05-10 Contact SGD

References cited on this page View Complete Literature Guide for AAC3
1) Kolarov J, et al.  (1990) A third ADP/ATP translocator gene in yeast. J Biol Chem 265(21):12711-6
2) Chen XJ  (2004) Sal1p, a calcium-dependent carrier protein that suppresses an essential cellular function associated With the Aac2 isoform of ADP/ATP translocase in Saccharomyces cerevisiae. Genetics 167(2):607-17
3) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
4) Lawson JE and Douglas MG  (1988) Separate genes encode functionally equivalent ADP/ATP carrier proteins in Saccharomyces cerevisiae. Isolation and analysis of AAC2. J Biol Chem 263(29):14812-8
5) Traba J, et al.  (2008) Yeast mitochondria import ATP through the calcium-dependent ATP-Mg/Pi carrier Sal1p, and are ATP consumers during aerobic growth in glucose. Mol Microbiol 69(3):570-85
6) Azuma M, et al.  (2008) Adenine nucleotide translocator transports haem precursors into mitochondria. PLoS One 3(8):e3070
7) Pereira C, et al.  (2007) ADP/ATP carrier is required for mitochondrial outer membrane permeabilization and cytochrome c release in yeast apoptosis. Mol Microbiol 66(3):571-82
8) Dienhart MK and Stuart RA  (2008) The Yeast Aac2 Protein Exists in Physical Association with the Cytochrome bc1-COX Supercomplex and the TIM23 Machinery. Mol Biol Cell 19(9):3934-43
9) Claypool SM, et al.  (2008) Cardiolipin defines the interactome of the major ADP/ATP carrier protein of the mitochondrial inner membrane. J Cell Biol 182(5):937-50
10) Smith CP and Thorsness PE  (2008) The Molecular Basis for Relative Physiological Functionality of the ADP/ATP Carrier Isoforms in Saccharomyces cerevisiae. Genetics 179(3):1285-99
11) Chen XJ and Clark-Walker GD  (2000) The petite mutation in yeasts: 50 years on. Int Rev Cytol 194:197-238
12) Drgon T, et al.  (1991) ADP/ATP translocator is essential only for anaerobic growth of yeast Saccharomyces cerevisiae. FEBS Lett 289(2):159-62
13) Fontanesi F, et al.  (2004) Mutations in AAC2, equivalent to human adPEO-associated ANT1 mutations, lead to defective oxidative phosphorylation in Saccharomyces cerevisiae and affect mitochondrial DNA stability. Hum Mol Genet 13(9):923-34
14) Chen XJ  (2002) Induction of an unregulated channel by mutations in adenine nucleotide translocase suggests an explanation for human ophthalmoplegia. Hum Mol Genet 11(16):1835-43
15) Palmieri L, et al.  (2005) Complete loss-of-function of the heart/muscle-specific adenine nucleotide translocator is associated with mitochondrial myopathy and cardiomyopathy. Hum Mol Genet 14(20):3079-88