Yeast ADP/ATP carrier (AAC) proteins exhibit similar enzymatic properties but their deletion produces different phenotypes

Drgon, Tomás; Sabová, L; Gavurníková, Gabriela; Kolarov, Jordan

doi:10.1016/0014-5793(92)80637-v

Cited by 37 publications

(28 citation statements)

References 10 publications

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“…However, only the disruption of AAC2 triggers a growth phenotype when the yeast is grown on nonfermentable carbon sources (72). Notably, in the absence of AAC2, the downregulation of the ADP/ATP exchange across the mt inner membrane is followed by a reduction in oxygen consumption and a decrease in complex IV activity (9).…”

Section: Discussionmentioning

confidence: 99%

The ADP/ATP Carrier and Its Relationship to Oxidative Phosphorylation in Ancestral Protist Trypanosoma brucei

et al. 2015

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The highly conserved ADP/ATP carrier (AAC) is a key energetic link between the mitochondrial (mt) and cytosolic compartments of all aerobic eukaryotic cells, as it exchanges the ATP generated inside the organelle for the cytosolic ADP. Trypanosoma brucei, a parasitic protist of medical and veterinary importance, possesses a single functional AAC protein (TbAAC) that is related to the human and yeast ADP/ATP carriers. However, unlike previous studies performed with these model organisms, this study showed that TbAAC is most likely not a stable component of either the respiratory supercomplex III؉IV or the ATP synthasome but rather functions as a physically separate entity in this highly diverged eukaryote. Therefore, TbAAC RNA interference (RNAi) ablation in the insect stage of T. brucei does not impair the activity or arrangement of the respiratory chain complexes. Nevertheless, RNAi silencing of TbAAC caused a severe growth defect that coincides with a significant reduction of mt ATP synthesis by both substrate and oxidative phosphorylation. Furthermore, TbAAC downregulation resulted in a decreased level of cytosolic ATP, a higher mt membrane potential, an elevated amount of reactive oxygen species, and a reduced consumption of oxygen in the mitochondria. Interestingly, while TbAAC has previously been demonstrated to serve as the sole ADP/ATP carrier for ADP influx into the mitochondria, our data suggest that a second carrier for ATP influx may be present and active in the T. brucei mitochondrion. Overall, this study provides more insight into the delicate balance of the functional relationship between TbAAC and the oxidative phosphorylation (OXPHOS) pathway in an early diverged eukaryote. The origination event of an ADP/ATP carrier (AAC) was crucial in the evolution of the present-day mitochondrion that enabled it to become the powerhouse of the eukaryotic cell. Due to the activity of AAC, the energy-producing mitochondria can supply the cytosol with ATP molecules, which fuel most cellular reactions. AAC belongs to the well-defined family of mitochondrial (mt) carrier proteins that are located in the inner mt membrane and are involved in the transport of a wide range of metabolites (1). Under physiological aerobic conditions, AAC is responsible for the 1:1 counterexchange of mt ATP for cytosolic ADP (2). mt ATP is produced mainly by the evolutionarily conserved biochemical pathway of oxidative phosphorylation (OXPHOS), which employs respiratory complexes I through IV to convert the redox energy of various mt substrates into an electrochemical proton gradient (⌬m) across the mt inner membrane. Respiratory complexes I (NADH-ubiquinone oxidoreductase) and II (succinate-ubiquinone oxidoreductase) are responsible for the oxidation of reduced NADH and FADH 2 , respectively. The electrons derived from these biochemical processes continue along the electron transport chain as they are sequentially passed to coenzyme Q, complex III (ubiquinol-cytochrome c oxidoreductase), cytochrome c, complex IV (cytochrome c-O 2 oxid...

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Section: Discussionmentioning

confidence: 99%

The ADP/ATP Carrier and Its Relationship to Oxidative Phosphorylation in Ancestral Protist Trypanosoma brucei

et al. 2015

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“…This hypothesis is supported by a kinetic analysis of the ADP/ATP-carrier (ACC1-3) of yeast. Here, the nucleotide transport rate of ACC1 protein is approximately 40% of the ACC2 nucleotide transport rate [19,20]. In the mammalian heart, an elevated ANT protein density that are four times higher than in the liver [18,21] may compensate the lower ANT1 isoform transport rate.…”

Section: Discussionmentioning

confidence: 99%

Tissue‐specific transcription pattern of the adenine nucleotide translocase isoforms in humans

et al. 1997

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Three adenine nucleotide translocase isoforms (ANT1, ANT2 and ANT3) are coded by different genes. The relative amounts of the three ANT isoform mRNAs were determined in detail in various human tissues. ANT isoforms were co-expressed in all tested tissues revealing tissue-specific transcription patterns. The highest ANT1 mRNA proportions were found in terminally differentiated tissues like skeletal muscle, heart and brain, whereas ANT2 was mainly expressed in tissues capable of proliferation and regeneration as in the kidneys, spleen, liver, fibroblasts and lymphocytes. The ANT3 mRNA proportion was not prominently expressed in any of the tissues tested. In conclusion, tissue-specific expression of ANT isoforms is strongly related to the state of cellular differentiation.

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“…A human VDAC1-expressing DVDAC yeast strain was produced by transfecting human vdac1 cDNA using lithium acetate with TRP selection (Shimizu et al, 1999). The ANT3-de®cient yeast strain (DANT3) (WD3, MATa ade2-1 his3-11,15 leu2-3,112 trp1-1 can1-100 aac3::URA3) and its parent strain (W303-1B, MATa ade2-1 his3-11,15 leu2-3,112 trp1-1 ura3-1 can1-100) were kind gifts from Dr MG Douglas (University of North Carolina, North Carolina, USA) (Drgon et al, 1992). Disruption of ANT1 and ANT2 in the WD3 strain was performed by homologous recombination with the respective targeting linear DNA fragments, as described previously (Hashimoto et al, 1999).…”

Section: Yeast Strainsmentioning

confidence: 99%

Bax and Bcl-xL independently regulate apoptotic changes of yeast mitochondria that require VDAC but not adenine nucleotide translocator

2000

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Mitochondria play an essential role in apoptosis by releasing apoptogenic molecules such as cytochrome c and AIF, and some caspases, which are all regulated by Bcl-2 family proteins. Pro-apoptotic Bax and Bak have been shown to induce cytochrome c release and loss of membrane potential (Dc) leading to AIF release in the isolated mitochondria. We have previously shown that Bax and Bak open the voltage-dependent anion channel (VDAC) allowing cytochrome c to pass through the channel, and Bcl-x L closes the channel. However, it has been reported that it is adenine nucleotide translocator (ANT) with which Bax/Bcl-x L interacts that modulate the channel activity. Here, we investigated the role of ANT and VDAC in the changes of isolated mitochondria triggered by Bax and by chemicals that induce permeability transition (PT). In rat and yeast mitochondria, Bax did not a ect the ADP/ATP exchange activity of ANT. VDAC-de®cient but not ANT-de®cient yeast mitochondria showed resistance to cytochrome c release, Dc loss, and swelling caused by Bax and PT inducers. Bcl-x L showed similar inhibition of all these changes in ANTde®cient and wild type yeast mitochondria. Furthermore, Bax induces cytochrome c release in wild type yeast cells but not VDAC1-de®cient yeast cells. These data indicate that VDAC, but not ANT, is essential for apoptotic mitochondrial changes. The data also indicate that Bcl-x L and Bax possess an ability to regulate mitochondrial membrane permeability independently of other Bcl-2 family members.

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Yeast ADP/ATP carrier (AAC) proteins exhibit similar enzymatic properties but their deletion produces different phenotypes

Cited by 37 publications

References 10 publications

The ADP/ATP Carrier and Its Relationship to Oxidative Phosphorylation in Ancestral Protist Trypanosoma brucei

The ADP/ATP Carrier and Its Relationship to Oxidative Phosphorylation in Ancestral Protist Trypanosoma brucei

Tissue‐specific transcription pattern of the adenine nucleotide translocase isoforms in humans

Bax and Bcl-xL independently regulate apoptotic changes of yeast mitochondria that require VDAC but not adenine nucleotide translocator

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