MDL1/YLR188W Summary Help

Standard Name MDL1 1
Systematic Name YLR188W
Feature Type ORF, Verified
Description Mitochondrial inner membrane half-type ABC transporter; mediates export of peptides generated upon proteolysis of mitochondrial proteins; plays a role in the regulation of cellular resistance to oxidative stress (1, 2, 3, 4 and see Summary Paragraph)
Name Description MultiDrug resistance-Like 1
Chromosomal Location
ChrXII:528300 to 530387 | ORF Map | GBrowse
Gene Ontology Annotations All MDL1 GO evidence and references
  View Computational GO annotations for MDL1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 2 genes
Classical genetics
reduction of function
Large-scale survey
102 total interaction(s) for 77 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 2
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 1
  • Reconstituted Complex: 2
  • Two-hybrid: 2

Genetic Interactions
  • Dosage Rescue: 1
  • Negative Genetic: 82
  • Positive Genetic: 8
  • Synthetic Lethality: 1
  • Synthetic Rescue: 1

Expression Summary
Length (a.a.) 695
Molecular Weight (Da) 75,949
Isoelectric Point (pI) 10.61
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXII:528300 to 530387 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..2088 528300..530387 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 | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | TCDB | UniProtKB
Primary SGDIDS000004178

MDL1 and MDL2 encode members of the ATP-binding Cassette (ABC) transporter family that reside in the mitochondrial inner membrane (1, 2). They are classified as "half-molecule" family members because they are comprised of one transmembrane domain and one nucleotide-binding domain, in contrast to "full-size" family members in which this arrangement is repeated in tandem. Mdl1p and Mdl2p are similar to each other and to other ABC family members, in particular to human TAP1 and TAP2, which form a heterodimer that transports peptides from the cytoplasm into the endoplasmic reticulum (1). Defects in TAP1 and TAP2 are linked to bare lymphocyte syndrome (OMIM) and Wegener-like granulomatosis (OMIM).

Processing of Mdl1p during import into the mitochondrial inner membrane removes a 59-amino acid presequence (5). In the inner membrane, Mdl1p exists as a homodimer with the nucleotide-binding domains exposed to the mitochondrial matrix (2, 5). An mdl1 null mutation does not confer any obvious growth phenotypes and in particular does not affect respiratory growth; however, it does decrease the export of peptides 6-20 amino acids in length from mitochondria (2). Mutations in conserved regions of the ABC family (the Walker A or B motifs, or the C-loop motif) also block the export of such oligopeptides (2). These peptides are generated by the m-AAA protease (Afg3p and Yta12p) as it degrades unassembled or misfolded proteins in the mitochondrial matrix as part of the mitochondrial protein quality control system. The role of Mdl1p is thought to be the transport of these peptides across the inner membrane into the intermembrane space, from which they diffuse passively across the outer membrane through the TOM complex or via outer membrane channel proteins such as Por1p and Por2p (2). Purified Mdl1p reconstituted into liposomes does not transport random 8- or 23-amino acid peptides, suggesting that it may have a limited substrate specificity (6).

Null mutation or overexpression of MDL1 affects sensitivity to oxidative stress, and additionally the null mutant exhibits a genetic interaction with a null mutation in ATM1 encoding another mitochondrial ABC transporter that exports iron-sulfur clusters to the cytosol (3). These phenotypes could indicate a role for Mdl1p in oxidative stress resistance via export of peptides generated from the turnover of damaged proteins, or could indicate a functional interaction between Mdl1p and Atm1p (3).

Last updated: 2010-02-09 Contact SGD

References cited on this page View Complete Literature Guide for MDL1
1) Dean M, et al.  (1994) Mapping and sequencing of two yeast genes belonging to the ATP-binding cassette superfamily. Yeast 10(3):377-83
2) Young L, et al.  (2001) Role of the ABC transporter Mdl1 in peptide export from mitochondria. Science 291(5511):2135-8
3) Chloupkova M, et al.  (2003) MDL1 is a high copy suppressor of ATM1: evidence for a role in resistance to oxidative stress. J Mol Biol 331(1):155-65
4) Galluhn D and Langer T  (2004) Reversible assembly of the ATP-binding cassette transporter Mdl1 with the F1F0-ATP synthase in mitochondria. J Biol Chem 279(37):38338-45
5) Gompf S, et al.  (2007) Switching of the homooligomeric ATP-binding cassette transport complex MDL1 from post-translational mitochondrial import to endoplasmic reticulum insertion. FEBS J 274(20):5298-310
6) Hofacker M, et al.  (2007) Structural and Functional Fingerprint of the Mitochondrial ATP-binding Cassette Transporter Mdl1 from Saccharomyces cerevisiae. J Biol Chem 282(6):3951-61