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

Cavero, Santiago; Traba, Javier; Arco, Araceli del; Satrústegui, Jorgina

doi:10.1042/bj20050806

Cited by 50 publications

(80 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Locus 1: Within locus 1 ( Figures 3A and 5A), the SAL1 gene encodes a protein that appears to be a Ca 21 -dependent ATP-Mg/P i exchanger in the mitochondrial inner membrane (Cavero et al 2005;Traba et al 2008). Loss-of-function mutations in SAL1 result in decreased mtDNA transmission under certain growth conditions .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Polymorphisms in Multiple Genes Contribute to the Spontaneous Mitochondrial Genome Instability ofSaccharomyces cerevisiaeS288C Strains

et al. 2009

View full text Add to dashboard Cite

The mitochondrial genome (mtDNA) is required for normal cellular function; inherited and somatic mutations in mtDNA lead to a variety of diseases. Saccharomyces cerevisiae has served as a model to study mtDNA integrity, in part because it can survive without mtDNA. A measure of defective mtDNA in S. cerevisiae is the formation of petite colonies. The frequency at which spontaneous petite colonies arise varies by $100-fold between laboratory and natural isolate strains. To determine the genetic basis of this difference, we applied quantitative trait locus (QTL) mapping to two strains at the opposite extremes of the phenotypic spectrum: the widely studied laboratory strain S288C and the vineyard isolate RM11-1a. Four main genetic determinants explained the phenotypic difference. Alleles of SAL1, CAT5, and MIP1 contributed to the high petite frequency of S288C and its derivatives by increasing the formation of petite colonies. By contrast, the S288C allele of MKT1 reduced the formation of petite colonies and compromised the growth of petite cells. The former three alleles were found in the EM93 strain, the founder that contributed $88% of the S288C genome. Nearly all of the phenotypic difference between S288C and RM11-1a was reconstituted by introducing the common alleles of these four genes into the S288C background. In addition to the nuclear gene contribution, the source of the mtDNA influenced its stability. These results demonstrate that a few rare genetic variants with individually small effects can have a profound phenotypic effect in combination. Moreover, the polymorphisms identified in this study open new lines of investigation into mtDNA maintenance.

show abstract

Section: Resultsmentioning

confidence: 99%

“…SAL1 encodes a mitochondrial ATP carrier that transports ATP into the mitochondrial matrix through the mitochondrial inner membrane (Cavero et al 2005). Thus, the ATP imported into the matrix by Sal1 fuels the maintenance of DC.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in Multiple Genes Contribute to the Spontaneous Mitochondrial Genome Instability ofSaccharomyces cerevisiaeS288C Strains

et al. 2009

View full text Add to dashboard Cite

show abstract

“…This may have significant implications in the ability of SLC25A25-deficient mice to produce sufficient ATP under conditions of increased energy demand such as skeletal muscle contraction and thus is consistent with the reduced endurance phenotype earlier described. ATP-Mg 2ϩ /P i carriers possess Ca 2ϩ -binding motifs facing the extramitochondrial space, which allows regulation of the carrier transport activity by cytosolic Ca 2ϩ without the requirement of Ca 2ϩ entry in the organelle (25). In SLC25A25-deficient cells, the reduced Ca 2ϩ flux paralleled the decrease in the capacity for ATP synthesis.…”

Section: Slc25a25-deficient Mouse Embryonic Fibroblasts Showmentioning

confidence: 99%

Inactivation of the Mitochondrial Carrier SLC25A25 (ATP-Mg2+/Pi Transporter) Reduces Physical Endurance and Metabolic Efficiency in Mice

Anunciado‐Koza¹,

Zhang

Ukropec³

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

An ATP-Mg 2؉/ P i inner mitochondrial membrane solute transporter (SLC25A25), which is induced during adaptation to cold stress in the skeletal muscle of mice with defective UCP1/ brown adipose tissue thermogenesis, has been evaluated for its role in metabolic efficiency. SLC25A25 is thought to control ATP homeostasis by functioning as a Ca 2؉ -regulated shuttle of ATP-Mg 2؉ and P i across the inner mitochondrial membrane. Mice with an inactivated Slc25a25 gene have reduced metabolic efficiency as evidenced by enhanced resistance to diet-induced obesity and impaired exercise performance on a treadmill. Obesity and its associated co-morbidities develop from a prolonged energy imbalance that occurs when food intake exceeds energy expenditure. Although considerable progress has been made in our understanding of the food intake side of the energy balance equation (1), much less is known of mechanisms of energy expenditure that can be utilized to reduce a positive energy balance. Two major thermogenic systems are known that can be activated voluntarily to increase energy expenditure. One is brown adipose tissue that functions to regulate body temperature and will be activated or not depending in part on whether a person chooses to become exposed to and to tolerate a reduced ambient temperature. The other is skeletal muscle, which functions primarily for motility, but is a major site for caloric expenditure and can be recruited to reduce excessive caloric stores. Although either exposure to reduced ambient temperature or physical activity can increase energy expenditure to maintain energy balance (2, 3), the modern lifestyle of many individuals does not support these natural antiobesity solutions. Mouse embryo fibroblasts fromGiven that skeletal muscle comprises up to 40% of total body weight and is able to consume 90% of the whole body oxygen uptake during maximal physical activity (4), the positive energy balance of obese individuals could be determined by variations in the efficiency of muscle energy metabolism (5). Mutations to several genes encoding and/or regulating the sarcoendoplasmic reticulum Ca 2ϩ -ATPases (SERCAs) 4 show deleterious phenotypes caused by defective Ca 2ϩ cycling, energy metabolism, and muscle function (6 -8); however, very few of these mutations have been analyzed for their impact on susceptibility to obesity and type 2 diabetes. Although the suppression of oxidative phosphorylation by reducing the number of mitochondria has been proposed to provide the conditions for the development of obesity and type 2 diabetes (5), in fact such suppression, as occurs with a skeletal muscle-specific inactivation of PGC-1␣, leads to mice with a lean body composition and resistance to diet-induced obesity (9). Therefore PGC-1␣-deficient mice are similar to UCP1-deficient mice in that a reduction in the capacity for energy expenditure and reduced mitochondrial function paradoxically reduces susceptibility to environmental obesity (10).It is generally observed that the inactivation of genes of energy metaboli...

show abstract

“…uptake, indicating that Sal1 is responsible for the influx of ATP into the matrix during glucose-based growth (Cavero et al 2005). Additionally, sal1D aac2D yeast are inviable (Chen 2004), presumably because in the absence of both proteins the rate of ATP import is too low to support growth.…”

Section: R96hmentioning

confidence: 99%

The Molecular Basis for Relative Physiological Functionality of the ADP/ATP Carrier Isoforms in Saccharomyces cerevisiae

Smith

Thorsness

2008

Genetics

View full text Add to dashboard Cite

AAC2 is one of three paralogs encoding mitochondrial ADP/ATP carriers in the yeast Saccharomyces cerevisiae, and because it is required for respiratory growth it has been the most extensively studied. To comparatively examine the relative functionality of Aac1, Aac2, and Aac3 in vivo, the gene encoding each isoform was expressed from the native AAC2 locus in aac1D aac3D yeast. Compared to Aac2, Aac1 exhibited reduced capacity to support growth of yeast lacking mitochondrial DNA or of yeast lacking the ATP/Mg-P i carrier, both conditions requiring ATP import into the mitochondrial matrix through the ADP/ATP carrier. Sixteen AAC1/AAC2 chimeric genes were constructed and analyzed to determine the key differences between residues or sections of Aac1 and Aac2. On the basis of the growth rate differences of yeast expressing different chimeras, the C1 and M2 loops of the ADP/ATP carriers contain divergent residues that are responsible for the difference(s) between Aac1 and Aac2. One chimeric gene construct supported growth on nonfermentable carbon sources but failed to support growth of yeast lacking mitochondrial DNA. We identified nine independent intragenic mutations in this chimeric gene that suppressed the growth phenotype of yeast lacking mitochondrial DNA, identifying regions of the carrier important for nucleotide exchange activities.

show abstract

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

Cited by 50 publications

References 43 publications

Polymorphisms in Multiple Genes Contribute to the Spontaneous Mitochondrial Genome Instability ofSaccharomyces cerevisiaeS288C Strains

Polymorphisms in Multiple Genes Contribute to the Spontaneous Mitochondrial Genome Instability ofSaccharomyces cerevisiaeS288C Strains

Inactivation of the Mitochondrial Carrier SLC25A25 (ATP-Mg2+/Pi Transporter) Reduces Physical Endurance and Metabolic Efficiency in Mice

The Molecular Basis for Relative Physiological Functionality of the ADP/ATP Carrier Isoforms in Saccharomyces cerevisiae

Contact Info

Product

Resources

About