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Gene Review

ATM1  -  ATP-binding cassette Fe/S cluster...

Saccharomyces cerevisiae S288c

Synonyms: Iron-sulfur clusters transporter ATM1, mitochondrial, MDY, YM9952.03C, YMR301C
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Disease relevance of ATM1


High impact information on ATM1

  • Additionally, when the ATM1 3' UTR was replaced by the ADH1 3' UTR, we obtained cells in which ATM1 mRNA is also delocalized, and presenting a respiratory dysfunction [5].
  • The ATP-binding cassette (ABC) transporter Atm1p of the mitochondrial inner membrane performs an essential function only in the generation of cytosolic Fe/S proteins by mediating export of Fe/S cluster precursors synthesized by Nfs1p and other mitochondrial proteins [6].
  • Cells lacking a functional ATM1 gene have an unstable mitochondrial genome and have white mitochondria that completely lack cytochromes [7].
  • This gene, ABC7, is an ortholog of the yeast ATM1 gene whose product localizes to the mitochondrial inner membrane and is involved in iron homeostasis [8].
  • Aft2 is activated at a later time in Atm1-depleted cells [9].

Biological context of ATM1


Anatomical context of ATM1

  • We have isolated a high copy suppressor of a temperature-sensitive mutation in ATM1, which codes for an ABC transporter of Saccharomyces cerevisiae mitochondria [12].
  • Since the function of the mitochondrial iron-sulfur cluster (ISC) assembly machinery is also required for these two processes, Atm1p is thought to translocate a still unknown product of this pathway to the cytosol [13].
  • In an attempt to evaluate the possible involvement of mitochondrion in vacuole function, a functional analysis of atm1(+) was performed by gene disruption [14].

Associations of ATM1 with chemical compounds

  • A double mutant in GSH1 and ATM1 encoding a mitochondrial ATP binding cassette (ABC) transporter involved in cytosolic Fe/S protein maturation is nonviable even in the presence of dithiothreitol [15].
  • Analysis of the effects of free iron and malonic acid (an inhibitor of oxidative respiration in mitochondria) on the incidence of petites among the mutant cells indicated that spontaneous induction of petites was a consequence of oxidative stress rather than a direct effect of either a defect in the ATM1 gene or the accumulation of free iron [11].
  • Similar to atm1 and other mutants defective in cytosolic Fe/S protein maturation, mitochondria from glutathione-depleted Deltagsh1 cells accumulated high amounts of iron [15].
  • Reconstitution of Atm1p into proteoliposomes allowed us to determine the biochemical characteristics of the ATPase such as: (i) the strong inhibition by the transition state analogue vanadate, (ii) a Km value of 0.1 mM, and (iii) a turnover number of 127 min-1 [13].
  • The ATPase activity of Atm1p is sensitive to sodium vanadate, a P-type ATPase inhibitor, with an IC(50) of 4 muM [16].

Other interactions of ATM1

  • One of the genes we identified was MDL1, which like ATM1, encodes a mitochondrial inner membrane ABC transporter [1].
  • PSE1/KAP121 overexpression also improves the import of the hydrophobic protein Atm1p, an ABC transporter of the mitochondrial inner membrane [17].
  • In spite of their apparent roles in cellular iron homeostasis, we find that the expression of neither ATM1 nor YFH1 is responsive to cellular iron status [2].
  • Thus, iron sensing by Aft1/Aft2 is not linked to the maturation of cytosolic/nuclear Fe-S proteins, but the mitochondrial inner membrane transporter Atm1 is important to transport the inhibitory signal [9].


  1. MDL1 is a high copy suppressor of ATM1: evidence for a role in resistance to oxidative stress. Chloupková, M., LeBard, L.S., Koeller, D.M. J. Mol. Biol. (2003) [Pubmed]
  2. The role of the mitochondrion in cellular iron homeostasis. Schueck, N.D., Woontner, M., Koeller, D.M. Mitochondrion (2001) [Pubmed]
  3. Characterization of the soluble domain of the ABC7 type transporter Atm1. Chen, C.A., Cowan, J.A. J. Biol. Chem. (2003) [Pubmed]
  4. The ABC transporter Atm1p is required for mitochondrial iron homeostasis. Kispal, G., Csere, P., Guiard, B., Lill, R. FEBS Lett. (1997) [Pubmed]
  5. In Saccharomyces cerevisiae, ATP2 mRNA sorting to the vicinity of mitochondria is essential for respiratory function. Margeot, A., Blugeon, C., Sylvestre, J., Vialette, S., Jacq, C., Corral-Debrinski, M. EMBO J. (2002) [Pubmed]
  6. The mitochondrial proteins Atm1p and Nfs1p are essential for biogenesis of cytosolic Fe/S proteins. Kispal, G., Csere, P., Prohl, C., Lill, R. EMBO J. (1999) [Pubmed]
  7. An ABC transporter in the mitochondrial inner membrane is required for normal growth of yeast. Leighton, J., Schatz, G. EMBO J. (1995) [Pubmed]
  8. Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A). Allikmets, R., Raskind, W.H., Hutchinson, A., Schueck, N.D., Dean, M., Koeller, D.M. Hum. Mol. Genet. (1999) [Pubmed]
  9. Activation of the iron regulon by the yeast Aft1/Aft2 transcription factors depends on mitochondrial but not cytosolic iron-sulfur protein biogenesis. Rutherford, J.C., Ojeda, L., Balk, J., Mühlenhoff, U., Lill, R., Winge, D.R. J. Biol. Chem. (2005) [Pubmed]
  10. MTABC3, a novel mitochondrial ATP-binding cassette protein involved in iron homeostasis. Mitsuhashi, N., Miki, T., Senbongi, H., Yokoi, N., Yano, H., Miyazaki, M., Nakajima, N., Iwanaga, T., Yokoyama, Y., Shibata, T., Seino, S. J. Biol. Chem. (2000) [Pubmed]
  11. A mutation in a mitochondrial ABC transporter results in mitochondrial dysfunction through oxidative damage of mitochondrial DNA. Senbongi, H., Ling, F., Shibata, T. Mol. Gen. Genet. (1999) [Pubmed]
  12. Mitochondrial and cytosolic branched-chain amino acid transaminases from yeast, homologs of the myc oncogene-regulated Eca39 protein. Kispal, G., Steiner, H., Court, D.A., Rolinski, B., Lill, R. J. Biol. Chem. (1996) [Pubmed]
  13. Stimulation of the ATPase activity of the yeast mitochondrial ABC transporter Atm1p by thiol compounds. Kuhnke, G., Neumann, K., Mühlenhoff, U., Lill, R. Mol. Membr. Biol. (2006) [Pubmed]
  14. Mitochondrial ABC transporter Atm1p is required for protection against oxidative stress and vacuolar functions in Schizosaccharomyces pombe. Iwaki, T., Fujita, Y., Tanaka, N., Giga-Hama, Y., Takegawa, K. Biosci. Biotechnol. Biochem. (2005) [Pubmed]
  15. Maturation of cytosolic iron-sulfur proteins requires glutathione. Sipos, K., Lange, H., Fekete, Z., Ullmann, P., Lill, R., Kispal, G. J. Biol. Chem. (2002) [Pubmed]
  16. Characterization of Saccharomyces cerevisiae Atm1p. Functional studies of an ABC7 type transporter. Chen, C.A., Cowan, J.A. Biochim. Biophys. Acta (2006) [Pubmed]
  17. Overexpression of yeast karyopherin Pse1p/Kap121p stimulates the mitochondrial import of hydrophobic proteins in vivo. Corral-Debrinski, M., Belgareh, N., Blugeon, C., Claros, M.G., Doye, V., Jacq, C. Mol. Microbiol. (1999) [Pubmed]
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