ATP-MgPi carrier activity in rat liver mitochondria

Nosek, Michael T.; Aprille, June R.

doi:10.1016/0003-9861(92)90628-a

Cited by 41 publications

(45 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…30 µM. The S 0.5 for calcium-activation of yeast Sal1p is somewhat higher than that reported for the rat liver carrier [28,29]. This is perhaps not so surprising as Sal1p lacks two (out of four) canonical EF-hand motifs that are present in human SCaMCs ( Figure 3C) [5].…”

Section: Activation By Calcium Of Atp Uptakementioning

confidence: 79%

The calcium-dependent ATP-Mg/Pi mitochondrial carrier is a target of glucose-induced calcium signalling in Saccharomyces cerevisiae

Cavero

Traba

Arco

et al. 2005

Biochemical Journal

View full text Add to dashboard Cite

Sal1p is a mitochondrial protein that belongs to the SCaMC (short calcium-binding mitochondrial carrier) subfamily of mitochondrial carriers. The presence of calcium-binding motifs facing the extramitochondrial space allows the regulation of the transport activity of these carriers by cytosolic calcium and provides a new mechanism to transduce calcium signals in mitochondria without the requirement of calcium entry in the organelle. We have studied its transport activity, finding that it is a carboxyatractylosideresistant ATP-Mg carrier. Mitochondria from a disruption mutant of SAL1 have a 50 % reduction in the uptake of ATP. We have also found a clear stimulation of ATP-transport activity by calcium, with an S 0.5 of approx. 30 µM. Our results also suggest that Sal1p is a target of the glucose-induced calcium signal which is nonessential in wild-type cells, but becomes essential for transport of ATP into mitochondria in yeast lacking ADP/ATP translocases.

show abstract

Section: Activation By Calcium Of Atp Uptakementioning

confidence: 79%

The calcium-dependent ATP-Mg/Pi mitochondrial carrier is a target of glucose-induced calcium signalling in Saccharomyces cerevisiae

Cavero

Traba

Arco

et al. 2005

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…1) with the phosphate groups interacting with R242 (22 BtAAC1 ) and K314 (79 BtAAC1 ) at contact point I and the adenine moiety in a hydrophobic pocket formed by G416 and I417 (182-183 BtAAC1 ) at contact point II. At contact point I of Sal1p, the phosphate-coordinated magnesium cation interacts with E318 (83 BtAAC1 ), whereas in BtAAC1 a threonine is in the equivalent position, which explains why Sal1p transports MgATP rather than ADP (14). Similarly, in Flx1p the flavin ring forms an aromatic stacking interaction with W88 (84 BtAAC1 ) and Y91 (87 BtAAC1 ) at contact point I, the adenine ring of FAD occupies the hydrophobic pocket formed by G193 and V194 (182-183 BtAAC1 ) at contact point II and its ␤-phosphate interacts with K237 (220 BtAAC1 ) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial carriers in the cytoplasmic state have a common substrate binding site

Robinson

Kunji

2006

Proc. Natl. Acad. Sci. U.S.A.

240

289

View full text Add to dashboard Cite

Mitochondrial carriers link biochemical pathways in the cytosol and mitochondrial matrix by transporting substrates across the inner mitochondrial membrane. Substrate recognition is specific for each carrier, but sequence similarities suggest the carriers have similar structures and mechanisms of substrate translocation. By considering conservation of amino acids, distance and chemical constraints, and by modeling family members on the known structure of the ADP͞ATP translocase, we have identified a common substrate binding site. It explains substrate selectivity and proton coupling and provides a mechanistic link to carrier opening by substrate-induced perturbation of the salt bridges that seal the pathway to and from the mitochondrial matrix. It enables the substrate specificity of uncharacterized mitochondrial carriers to be predicted.comparative modeling ͉ membrane protein ͉ sequence alignment M embers of the mitochondrial carrier family are located in the inner mitochondrial membrane and allow exchange of substrates between the cytosol and the mitochondrial matrix (1). The family is exclusive to eukaryotes, and its members are unrelated to other transporter families, including the major facilitator superfamily and the ABC transporters. Their substrates include nucleotides, amino acids, cofactors, carboxylic acids, and inorganic anions required by the organelle for oxidative phosphorylation, gluconeogenesis, synthesis and degradation of amino and fatty acids, macromolecular synthesis of proteins and nucleic acids, sterol metabolism, and thermogenesis (1). Mutations of the carriers are associated with diseases, including progressive external opthalmoplegia, adult-and neonatal-onset type II citrullinaemia, Amish-type microcephaly, hyperornithinemia-hyperammonia-homocitrullinuria, carnitineacylcarnitine translocase deficiency, neonatal myoclonic epilepsy, severe obesity, and type II diabetes (1).The mitochondrial carriers have three tandem repeats of Ϸ100 aa, each containing two transmembrane ␣-helices linked by a large loop (2) and a conserved signature motif P-X-[DE]-X-X-[RK] (3). The carriers exist in two distinct conformational states: the cytoplasmic state (c-state) in which the carrier accepts its substrate from the cytoplasm, and the matrix state in which it accepts a substrate from the mitochondrial matrix. For the ADP͞ATP carrier, the inhibitor carboxyatractyloside (CATR) is known to bind to the carrier in the c-state only and prevent the binding of ADP. In the atomic model of the ADP͞ATP carrier 1 from Bos taurus (BtAAC1) in complex with CATR (4), the six-transmembrane ␣-helices form a barrel that has pseudo-3-fold symmetry. CATR is bound in the internal aqueous cavity (see Fig. 4, which is published as supporting information on the PNAS web site), which is open to the cytosol and closed to the mitochondrial matrix, consistent with the structure representing the c-state. The prolines of the signature motif kink the transmembrane helices, bringing their C-terminal ends together at the base of the cavit...

show abstract

“…AdN depletion was confirmed by measuring oxygen consumption in the presence of 1 mM EGTA, as depleted mitochondria are unable to stimulate respiration after ADP addition (7). For the filling reactions with ATP-Mg, mitochondria were incubated in MSK devoid of EDTA and supplemented with 200 nM RR and the indicated concentrations of ATP and MgCl 2 , at 30°C for different lengths of time.…”

Section: Methodsmentioning

confidence: 99%

“…In the first, entry of cytosolic Ca 2ϩ into the mitochondria would inhibit the matrix pyrophosphatase, leading to an increase in pyrophosphate that would then be exchanged by cytosolic AdNs through the ATP/ADP translocase (ANT) (6). The second mechanism, proposed by Aprille and co-workers (7,8), involves the ATP-Mg/P i carrier, a Ca 2ϩ -dependent mitochondrial carrier that has been recently identified at the molecular level (9,10).…”

Section: It Has Been Known For a Long Time That Mitochondria Isolatedmentioning

confidence: 99%

“…Although the ATP-Mg/P i carrier can transport both ATP-Mg and ADP in isolated mitochondria and reconstituted liposomes, it has been shown that ATP-Mg is the preferred substrate under normal energized conditions, as the cytosolic ATP concentration exceeds that of ADP (36). To study the respiratory effect of ATP-Mg uptake in AdN-depleted mitochondria, these were incubated at 30°C in the presence of 2 mM ATP, 5 mM MgCl 2 , and 200 nM RR for different lengths of time, and then the ADP-response to oxygen consumption in the presence of 1 mM EGTA was evaluated.…”

Section: ϩmentioning

confidence: 99%

See 1 more Smart Citation

Glucagon Regulation of Oxidative Phosphorylation Requires an Increase in Matrix Adenine Nucleotide Content through Ca2+ Activation of the Mitochondrial ATP-Mg/Pi Carrier SCaMC-3

Amigo

Traba

Barroso

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Glucagon stimulates liver respiration. Results: SCaMC-3 is the only functional mitochondrial ATP-Mg/P i carrier in adult liver and SCaMC-3 deficiency prevents glucagon effects in hepatocytes and in vivo. Conclusion: SCaMC-3 is required for the stimulation of oxidative phosphorylation in response to glucagon through a Ca 2ϩ -dependent increase of mitochondrial adenine nucleotides and Ca 2ϩ retention. Significance: Ca 2ϩ stimulation of SCaMC-3 is required for liver response to glucagon.

show abstract

ATP-MgPi carrier activity in rat liver mitochondria

Cited by 41 publications

References 33 publications

The calcium-dependent ATP-Mg/Pi mitochondrial carrier is a target of glucose-induced calcium signalling in Saccharomyces cerevisiae

The calcium-dependent ATP-Mg/Pi mitochondrial carrier is a target of glucose-induced calcium signalling in Saccharomyces cerevisiae

Mitochondrial carriers in the cytoplasmic state have a common substrate binding site

Glucagon Regulation of Oxidative Phosphorylation Requires an Increase in Matrix Adenine Nucleotide Content through Ca2+ Activation of the Mitochondrial ATP-Mg/Pi Carrier SCaMC-3

Contact Info

Product

Resources

About