Biochemical characterization of a new mitochondrial transporter of dephosphocoenzyme A in Drosophila melanogaster.
- Authors
- Vozza, Angelo; De Leonardis, Francesco; Paradies, Eleonora; De Grassi, Anna; Pierri, Ciro Leonardo; Parisi, Giovanni; Marobbio, Carlo Marya Thomas; Lasorsa, Francesco Massimo; Muto, Luigina; Capobianco, Loredana; Dolce, Vincenza; Raho, Susanna; Fiermonte, Giuseppe
- Year
- 2017
- Journal
- Biochimica et biophysica acta. Bioenergetics
- PMID
- 27836698
- DOI
- 10.1016/j.bbabio.2016.11.006
CoA is an essential cofactor that holds a central role in cell metabolism. Although its biosynthetic pathway is conserved across the three domains of life, the subcellular localization of the eukaryotic biosynthetic enzymes and the mechanism behind the cytosolic and mitochondrial CoA pools compartmentalization are still under debate. In humans, the transport of CoA across the inner mitochondrial membrane has been ascribed to two related genes, SLC25A16 and SLC25A42 whereas in D. melanogaster genome only one gene is present, CG4241, phylogenetically closer to SLC25A42. CG4241 encodes two alternatively spliced isoforms, dPCoAC-A and dPCoAC-B. Both isoforms were expressed in Escherichia coli, but only dPCoAC-A was successfully reconstituted into liposomes, where transported dPCoA and, to a lesser extent, ADP and dADP but not CoA, which was a powerful competitive inhibitor. The expression of both isoforms in a Saccharomyces cerevisiae strain lacking the endogenous putative mitochondrial CoA carrier restored the growth on respiratory carbon sources and the mitochondrial levels of CoA. The results reported here and the proposed subcellular localization of some of the enzymes of the fruit fly CoA biosynthetic pathway, suggest that dPCoA may be synthesized and phosphorylated to CoA in the matrix, but it can also be transported by dPCoAC to the cytosol, where it may be phosphorylated to CoA by the monofunctional dPCoA kinase. Thus, dPCoAC may connect the cytosolic and mitochondrial reactions of the CoA biosynthetic pathway without allowing the two CoA pools to get in contact.
No figures extracted from this document.
No chunks β full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
No citations found.
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Genome-wide association study of stimulant dependence. | 2021 | 34226506 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Carnitine O-Acetyltransferase as a Central Player in Lipid and Branched-Chain Amino Acid Metabolism, Epigenetics, Cell Plasticity, and Organelle Function. | Volpicella M et al. | β | 2025 | β |
| Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. | Liu R et al. | β | 2025 | β |
| SLC25A mitochondrial carriers as biomarkers and therapeutic targets of spaceflight-induced dysfunction: the ADP/ATP carrier (AAC3) as a structural case study. | D'Addabbo P et al. | β | 2025 | β |
| Coenzyme A biosynthesis: mechanisms of regulation, function and disease. | Barritt SA et al. | β | 2024 | β |
| Human mitochondrial uncoupling protein 3 functions as a metabolite transporter. | De Leonardis F et al. | β | 2024 | β |
| Modulatory Effect of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) on the 2-Oxoglutarate Mitochondrial Carrier. | Spagnoletta A et al. | β | 2024 | β |
| The Role of Mitochondrial Solute Carriers SLC25 in Cancer Metabolic Reprogramming: Current Insights and Future Perspectives. | Ahmed A et al. | β | 2024 | β |
| Two functionally different mitochondrial phosphate carriers support Drosophila melanogaster OXPHOS throughout distinct developmental stages. | Curcio R et al. | β | 2024 | β |
| A small molecule 20C from Gastrodia elata inhibits Ξ±-synuclein aggregation and prevents progression of Parkinson's disease. | Peng Y et al. | β | 2023 | β |
| Generation of a Yeast Cell Model Potentially Useful to Identify the Mammalian Mitochondrial <i>N</i>-Acetylglutamate Transporter. | Gorgoglione R et al. | β | 2023 | β |
| Hyaluronic Acid: A Powerful Biomolecule with Wide-Ranging Applications-A Comprehensive Review. | Iaconisi GN et al. | β | 2023 | β |
| Inherited Disorders of Coenzyme A Biosynthesis: Models, Mechanisms, and Treatments. | Cavestro C et al. | β | 2023 | β |
| In Silico Analysis of the Structural Dynamics and Substrate Recognition Determinants of the Human Mitochondrial Carnitine/Acylcarnitine SLC25A20 Transporter. | Pasquadibisceglie A et al. | β | 2023 | β |
| Probing coenzyme A homeostasis with semisynthetic biosensors. | Xue L et al. | β | 2023 | β |
| Citrate Regulates the <i>Saccharomyces cerevisiae</i> Mitochondrial GDP/GTP Carrier (Ggc1p) by Triggering Unidirectional Transport of GTP. | Seccia R et al. | β | 2022 | β |
| Glutamine-Derived Aspartate Biosynthesis in Cancer Cells: Role of Mitochondrial Transporters and New Therapeutic Perspectives. | Gorgoglione R et al. | β | 2022 | β |
| <i>Drosophila melanogaster</i> Uncoupling Protein-4A (UCP4A) Catalyzes a Unidirectional Transport of Aspartate. | Lunetti P et al. | β | 2022 | β |
| Mitochondrial transport and metabolism of the vitamin B-derived cofactors thiamine pyrophosphate, coenzyme A, FAD and NAD<sup>+</sup> , and related diseases: A review. | Palmieri F et al. | β | 2022 | β |
| New Insights Regarding Hemin Inhibition of the Purified Rat Brain 2-Oxoglutarate Carrier and Relationships with Mitochondrial Dysfunction. | Miniero DV et al. | β | 2022 | β |
| Personalized Medicine in Mitochondrial Health and Disease: Molecular Basis of Therapeutic Approaches Based on Nutritional Supplements and Their Analogs. | Tragni V et al. | β | 2022 | β |
| PKAN pathogenesis and treatment. | Hayflick SJ et al. | β | 2022 | β |
| An Overview of Mitochondrial Protein Defects in Neuromuscular Diseases. | Marra F et al. | β | 2021 | β |
| Coenzyme a Biochemistry: From Neurodevelopment to Neurodegeneration. | Mignani L et al. | β | 2021 | β |
| Evaluating the Genetic Capacity of <i>Mycoplasmas</i> for Coenzyme A Biosynthesis in a Search for New Anti-mycoplasma Targets. | Ras TA et al. | β | 2021 | β |
| Genome-wide association study of stimulant dependence. | Cox J et al. | β | 2021 | β |
| Targeting mitochondrial metabolite transporters in Penicillium expansum for reducing patulin production. | Tragni V et al. | β | 2021 | β |
| The Interaction of Hemin, a Porphyrin Derivative, with the Purified Rat Brain 2-Oxoglutarate Carrier. | Miniero DV et al. | β | 2021 | β |
| The mitochondrial aspartate/glutamate carrier (AGC or Aralar1) isoforms in D. melanogaster: biochemical characterization, gene structure, and evolutionary analysis. | Lunetti P et al. | β | 2021 | β |
| Cloning, Purification, and Characterization of the Catalytic C-Terminal Domain of the Human 3-Hydroxy-3-methyl glutaryl-CoA Reductase: An Effective, Fast, and Easy Method for Testing Hypocholesterolemic Compounds. | Curcio R et al. | β | 2020 | β |
| Diseases Caused by Mutations in Mitochondrial Carrier Genes <i>SLC25</i>: A Review. | Palmieri F et al. | β | 2020 | β |
| <i>Drosophila melanogaster</i> Mitochondrial Carriers: Similarities and Differences with the Human Carriers. | Curcio R et al. | β | 2020 | β |
| KRAS-regulated glutamine metabolism requires UCP2-mediated aspartate transport to support pancreatic cancer growth. | Raho S et al. | β | 2020 | β |
| Regulation of coenzyme A levels by degradation: the 'Ins and Outs'. | Naquet P et al. | β | 2020 | β |
| Targeting <i>Penicillium expansum</i> GMC Oxidoreductase with High Affinity Small Molecules for Reducing Patulin Production. | Tragni V et al. | β | 2020 | β |
| Vitamin in the Crosshairs: Targeting Pantothenate and Coenzyme A Biosynthesis for New Antituberculosis Agents. | Butman HS et al. | β | 2020 | β |
| A Homozygous Splice Site Mutation in SLC25A42, Encoding the Mitochondrial Transporter of Coenzyme A, Causes Metabolic Crises and Epileptic Encephalopathy. | Iuso A et al. | β | 2019 | β |
| Functional characterization of the partially purified Sac1p independent adenine nucleotide transport system (ANTS) from yeast endoplasmic reticulum. | Li Y et al. | β | 2018 | β |
| Vnn1 pantetheinase limits the Warburg effect and sarcoma growth by rescuing mitochondrial activity. | Giessner C et al. | β | 2018 | β |
| Tissue-specific expression and silencing phenotypes of mitochondrial phosphate carrier paralogues in several insect species. | Sugahara R et al. | β | 2017 | β |