Disease relevance of MDL1

• We demonstrate that over-expression of MDL1 in Deltaatm1 cells results in a reduction of mitochondrial iron content, and decreased sensitivity to H(2)O(2) and transition metal toxicity [1].
• To characterize the ATP hydrolysis cycle of Mdl1p, the nucleotide-binding domain (NBD) was overexpressed in Escherichia coli and purified to homogeneity [2].

High impact information on MDL1

• Role of the ABC transporter Mdl1 in peptide export from mitochondria [3].
• Galectin-1 is exported across the yeast plasma membrane, and this export does not require the classical secretory pathway nor the yeast multidrug resistance-like protein Ste6p, the transporter for the peptide a factor [4].
• Multidrug resistance-like genes of Arabidopsis required for auxin transport and auxin-mediated development [5].
• After screening expression in various hosts, Mdl1 was overexpressed 100-fold to 1% of total mitochondrial membrane protein in S. cerevisiae [6].
• The ATP-binding cassette half-transporter Mdl1 from Saccharomyces cerevisiae has been proposed to be involved in the quality control of misassembled respiratory chain complexes by exporting degradation products generated by the m-AAA proteases from the matrix [6].

Biological context of MDL1

• MDL1 is a high copy suppressor of ATM1: evidence for a role in resistance to oxidative stress [1].
• On the other hand, deletion of MDL1, coding for an ABC-transporter involved in peptide export from the matrix space, only had minor effects on nuclear gene expression [7].
• The ATP hydrolysis cycle of the nucleotide-binding domain of the mitochondrial ATP-binding cassette transporter Mdl1p [2].
• The ABC transporter Mdl1p, a structural and functional homologue of the transporter associated with antigen processing (TAP) plays an important role in intracellular peptide transport from the mitochondrial matrix of Saccharomyces cerevisiae [2].
• These results are consistent with an activation of Mdl1 upon dissociation from the ATP synthase and suggest a link of peptide export from mitochondria to the activity of the F(1)F(0)-ATP synthase and the cellular energy metabolism [8].

Anatomical context of MDL1

• The function of the mitochondrial Mdl1/2p-like proteins is not clear at present with the notable exception of murine ABC-me that may transport intermediates of heme biosynthesis from the matrix to the cytosol in erythroid tissues [9].

Associations of MDL1 with chemical compounds

• Although independent of Mdl1 activity, complex formation is impaired upon inhibition of the F(1)F(0)-ATP synthase with oligomycin or N,N'-dicyclohexylcarbodiimide [8].

Other interactions of MDL1

• One of the genes we identified was MDL1, which like ATM1, encodes a mitochondrial inner membrane ABC transporter [1].
• The encoded protein is similar to those encoded by MDL1 and MDL2, two MDR-like genes of Saccharomyces cerevisiae [10].

References