Glutathione-coordinated [2Fe–2S] cluster: a viable physiological substrate for mitochondrial ABCB7 transport

Li, Jingwei; Cowan, J. A.

doi:10.1039/c4cc09175b

Cited by 66 publications

(63 citation statements)

References 26 publications

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“…Metal glutathione complexes have been proposed as trafficking ligands in eukaryotic cells. 37–39 Conceivably, these metal complexes might be related to [M(SG) 4 ] 2− which would have a mass of ca . 1300 Da.…”

Section: Discussionmentioning

confidence: 99%

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Detection of Labile Low-Molecular-Mass Transition Metal Complexes in Mitochondria

2015

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Liquid chromatography was used with an on-line inductively coupled plasma mass spectrometer to detect low-molecular-mass (LMM) transition metal complexes in mitochondria isolated from fermenting yeast cells, human Jurkat cells, and mouse brain and liver. These complexes constituted 20 – 40% of total mitochondrial Mn, Fe, Zn, and Cu ions. The major LMM Mn complex in yeast mitochondria had a mass of ca. 1100 Da and a concentration of ~ 2 μM. Mammalian mitochondria contained a second Mn species with a mass of ca. 2000 Da at a comparable concentration. The major Fe complex in mitochondria isolated from exponentially growing yeast cells had a mass of ca. 580 Da; the concentration of Fe580 in mitochondria was ca. 100 μM. When mitochondria were isolated from fermenting cells in post-exponential phase, the mass of the dominant LMM Fe complex was ca. 1100 Da. Upon incubation, the intensity of Fe1100 declined and Fe580 increased, suggesting that the two are interrelated. Mammalian mitochondria contained Fe580 and 2 other Fe species (Fe2000 and Fe1100) at concentrations of ca. 50 μM each. The dominant LMM Zn species in mitochondria had a mass of ca. 1200 Da and a concentration of ca. 110 μM. Mammalian mitochondria contained a second major LMM Zn species at 1500 Da. The dominant LMM Cu species in yeast mitochondria had a mass of ca. 5000 Da and a concentration in yeast mitochondria of ca. 16 μM; Cu5000 was not observed in mammalian mitochondria. The dominant Co species in mitochondria, Co1200, had a concentration of 20 nM and was probably a cobalamin. Mammalian but not yeast mitochondria contained a LMM Mo species, Mo730, at ca. 1 μM concentration. Increasing Mn, Fe, Cu, and Zn concentrations 10 fold in the medium increased the concentration of the same element in the corresponding isolated mitochondria. Treatment with metal chelators confirmed that these LMM species were labile. The dominant S species at 1100 Da was not free GSH or GSSG.

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Section: Discussionmentioning

confidence: 99%

“…7 However, the Cu ions that metallate IMS metalloproteins have been proposed to pass from the cytosol to the matrix and then to the IMS. 39 …”

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confidence: 99%

Detection of Labile Low-Molecular-Mass Transition Metal Complexes in Mitochondria

2015

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“…Most of the previous suggestions for the chemical identity of the Atm1 substrate X-S were based on in vitro studies using either ATPase stimulation approaches (Kuhnke et al, 2006;Qi et al, 2014) or transport experiments with Atm1-loaded vesicles or proteoliposomes (Li and Cowan, 2015;Schaedler et al, 2014). Confusingly, these approaches have led to rather different ideas for the identity of the potential Atm1 substrate (see above).…”

Section: Page 16 Of 40mentioning

confidence: 96%

“…Various methods were employed recording the appearance of iron or a fluorescein-labeled GSH inside the vesicles, and suggested a slow, but ATP-dependent uptake into the Atm1-containing liposomes (Li and Cowan, 2015). Because both the transport rate and efficiency are rather low (also relative to GSH), the in vivo relevance of these studies needs to be verified.…”

Section: Functional Analysis Of Atm1 Its Putative Substrate and Thementioning

confidence: 99%

The role of mitochondria and the CIA machinery in the maturation of cytosolic and nuclear iron–sulfur proteins

Lill

Dutkiewicz

Freibert

et al. 2015

European Journal of Cell Biology

161

179

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“…In more recent literature, a molecule containing persulfide 'X-S' has been favoured (see [41,42] and discussions therein). However, the idea of a glutathioneconjugated [2Fe-2S] cluster as a candidate substrate is also being tested in vitro [43,44].…”

Section: Abcb7 and Its Homologues In Different Eukaryotesmentioning

confidence: 99%

Structures and functions of mitochondrial ABC transporters

Schaedler

Faust

Shintre

et al. 2015

Biochemical Society Transactions

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A small number of physiologically important ATP-binding cassette (ABC) transporters are found in mitochondria. Most are half transporters of the B group forming homodimers and their topology suggests they function as exporters. The results of mutant studies point towards involvement in iron cofactor biosynthesis. In particular, ABC subfamily B member 7 (ABCB7) and its homologues in yeast and plants are required for iron-sulfur (Fe-S) cluster biosynthesis outside of the mitochondria, whereas ABCB10 is involved in haem biosynthesis. They also play a role in preventing oxidative stress. Mutations in ABCB6 and ABCB7 have been linked to human disease. Recent crystal structures of yeast Atm1 and human ABCB10 have been key to identifying substrate-binding sites and transport mechanisms. Combined with in vitro and in vivo studies, progress is being made to find the physiological substrates of the different mitochondrial ABC transporters. Sequence analysis of mitochondrial ABC transportersMitochondria of most eukaryote species harbour 2-4 different ABC transporters that belong to the B subfamily of half transporters. The proteins contain an N-terminal transmembrane domain (TMD) and a C-terminal nucleotidebinding domain (NBD), which form homodimers for full functionality [1]. Plant and algal genomes additionally encode a unique ABC transporter, termed cytochrome c maturation (Ccm)AB, in which the TMD and NBD are encoded by separate genes. CcmAB is placed in the ABCI subfamily, see section 'CcmAB in plant mitochondria'. Phylogenetic relationship of mitochondrial transporters of the ABCB subfamilyAs a starting point for the discussion of recent crystal structures and functional data, we have reanalysed the phylogenetic relationships of B-type mitochondrial ABC transporters and their closest prokaryotic homologues (Figure 1). The CcmAB proteins were excluded from the phylogenetic analysis due to their large evolutionary distance from the other mitochondrial ABC transporters.Key words: ATP-binding cassette (ABC) transporter, glutathione, haem, iron, mitochondria, oxidative stress. Abbreviations: ABC, ATP-binding cassette; Aft, Activator of ferrous transport; ATM, ABC transporter of the mitochondria; Ccm, cytochrome c maturation; dALA, δ-amino levulinic acid; IRP1, iron regulatory protein 1; Mdl, multi-drug resistance-like; Mfrn, mitoferrin; NBD, nt-binding domain; PPIX, protoporphyrin IX; TMD, transmembrane domain; TMH, transmembrane helix. 1 To whom correspondence should be addressed (email janneke.balk@jic.ac.uk).The ABCB7 group, which includes the ABC transporters of the mitochondria Atm1 in yeast and ATM3 in Arabidopsis, can be found in virtually all eukaryotic species. Human ABCB7 and Arabidopsis ATM3 can largely rescue the phenotypes of yeast atm1 mutants [2][3][4], providing experimental support that members of this subfamily may have the same function. Human ABCB6 can also partially complement a yeast atm1 mutant [5] but differences in the intracellular localization of ABCB6 and Atm1 may point to distinct phys...

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Glutathione-coordinated [2Fe–2S] cluster: a viable physiological substrate for mitochondrial ABCB7 transport

Cited by 66 publications

References 26 publications

Detection of Labile Low-Molecular-Mass Transition Metal Complexes in Mitochondria

Detection of Labile Low-Molecular-Mass Transition Metal Complexes in Mitochondria

The role of mitochondria and the CIA machinery in the maturation of cytosolic and nuclear iron–sulfur proteins

Structures and functions of mitochondrial ABC transporters

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