Depletion of ATP-Citrate Lyase (ATPCL) Affects Chromosome Integrity Without Altering Histone Acetylation in Drosophila Mitotic Cells
The Citrate Lyase (ACL) is the main cytosolic enzyme that converts the citrate exported from mitochondria by the SLC25A1 carrier in Acetyl Coenzyme A (acetyl-CoA) and oxaloacetate. Acetyl-CoA is a high-energy intermediate common to a large number of metabolic processes including protein acetylation...
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Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2019.00383/full |
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| author | Patrizia Morciano Maria Laura Di Giorgio Antonella Porrazzo Antonella Porrazzo Valerio Licursi Rodolfo Negri Rodolfo Negri Yikang Rong Giovanni Cenci Giovanni Cenci |
| author_facet | Patrizia Morciano Maria Laura Di Giorgio Antonella Porrazzo Antonella Porrazzo Valerio Licursi Rodolfo Negri Rodolfo Negri Yikang Rong Giovanni Cenci Giovanni Cenci |
| author_sort | Patrizia Morciano |
| collection | DOAJ |
| description | The Citrate Lyase (ACL) is the main cytosolic enzyme that converts the citrate exported from mitochondria by the SLC25A1 carrier in Acetyl Coenzyme A (acetyl-CoA) and oxaloacetate. Acetyl-CoA is a high-energy intermediate common to a large number of metabolic processes including protein acetylation reactions. This renders ACL a key regulator of histone acetylation levels and gene expression in diverse organisms including humans. We have found that depletion of ATPCL, the Drosophila ortholog of human ACL, reduced levels of Acetyl CoA but, unlike its human counterpart, does not affect global histone acetylation and gene expression. Nevertheless, reduced ATPCL levels caused evident, although moderate, mitotic chromosome breakage suggesting that this enzyme plays a partial role in chromosome stability. These defects did not increase upon X-ray irradiation, indicating that they are not dependent on an impairment of DNA repair. Interestingly, depletion of ATPCL drastically increased the frequency of chromosome breaks (CBs) associated to mutations in scheggia, which encodes the ortholog of the mitochondrial citrate carrier SLC25A1 that is also required for chromosome integrity and histone acetylation. Our results indicate that ATPCL has a dispensable role in histone acetylation and prevents massive chromosome fragmentation when citrate efflux is altered. |
| first_indexed | 2024-12-21T22:37:40Z |
| format | Article |
| id | doaj.art-3d10e0a0e3f04498b2ae9a9de2856807 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-21T22:37:40Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-3d10e0a0e3f04498b2ae9a9de28568072022-12-21T18:47:55ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-04-011010.3389/fphys.2019.00383445800Depletion of ATP-Citrate Lyase (ATPCL) Affects Chromosome Integrity Without Altering Histone Acetylation in Drosophila Mitotic CellsPatrizia Morciano0Maria Laura Di Giorgio1Antonella Porrazzo2Antonella Porrazzo3Valerio Licursi4Rodolfo Negri5Rodolfo Negri6Yikang Rong7Giovanni Cenci8Giovanni Cenci9Dipartimento di Biologia e Biotecnologie “Charles Darwin”, Sapienza – Università di Roma, Rome, ItalyDipartimento di Biologia e Biotecnologie “Charles Darwin”, Sapienza – Università di Roma, Rome, ItalyDipartimento di Biologia e Biotecnologie “Charles Darwin”, Sapienza – Università di Roma, Rome, ItalyIstituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, ItalyIstituto di Analisi dei Sistemi ed Informatica “Antonio Ruberti”, Consiglio Nazionale delle Ricerche, Rome, ItalyDipartimento di Biologia e Biotecnologie “Charles Darwin”, Sapienza – Università di Roma, Rome, ItalyIstituto di Biologia e Patologia Molecolari (IBPM) del CNR, Rome, ItalySchool of Life Sciences, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou, ChinaDipartimento di Biologia e Biotecnologie “Charles Darwin”, Sapienza – Università di Roma, Rome, ItalyIstituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, ItalyThe Citrate Lyase (ACL) is the main cytosolic enzyme that converts the citrate exported from mitochondria by the SLC25A1 carrier in Acetyl Coenzyme A (acetyl-CoA) and oxaloacetate. Acetyl-CoA is a high-energy intermediate common to a large number of metabolic processes including protein acetylation reactions. This renders ACL a key regulator of histone acetylation levels and gene expression in diverse organisms including humans. We have found that depletion of ATPCL, the Drosophila ortholog of human ACL, reduced levels of Acetyl CoA but, unlike its human counterpart, does not affect global histone acetylation and gene expression. Nevertheless, reduced ATPCL levels caused evident, although moderate, mitotic chromosome breakage suggesting that this enzyme plays a partial role in chromosome stability. These defects did not increase upon X-ray irradiation, indicating that they are not dependent on an impairment of DNA repair. Interestingly, depletion of ATPCL drastically increased the frequency of chromosome breaks (CBs) associated to mutations in scheggia, which encodes the ortholog of the mitochondrial citrate carrier SLC25A1 that is also required for chromosome integrity and histone acetylation. Our results indicate that ATPCL has a dispensable role in histone acetylation and prevents massive chromosome fragmentation when citrate efflux is altered.https://www.frontiersin.org/article/10.3389/fphys.2019.00383/fullcitrate lyaseDrosophila chromosomeshistone acetylationacetyl-CoADrosophila |
| spellingShingle | Patrizia Morciano Maria Laura Di Giorgio Antonella Porrazzo Antonella Porrazzo Valerio Licursi Rodolfo Negri Rodolfo Negri Yikang Rong Giovanni Cenci Giovanni Cenci Depletion of ATP-Citrate Lyase (ATPCL) Affects Chromosome Integrity Without Altering Histone Acetylation in Drosophila Mitotic Cells Frontiers in Physiology citrate lyase Drosophila chromosomes histone acetylation acetyl-CoA Drosophila |
| title | Depletion of ATP-Citrate Lyase (ATPCL) Affects Chromosome Integrity Without Altering Histone Acetylation in Drosophila Mitotic Cells |
| title_full | Depletion of ATP-Citrate Lyase (ATPCL) Affects Chromosome Integrity Without Altering Histone Acetylation in Drosophila Mitotic Cells |
| title_fullStr | Depletion of ATP-Citrate Lyase (ATPCL) Affects Chromosome Integrity Without Altering Histone Acetylation in Drosophila Mitotic Cells |
| title_full_unstemmed | Depletion of ATP-Citrate Lyase (ATPCL) Affects Chromosome Integrity Without Altering Histone Acetylation in Drosophila Mitotic Cells |
| title_short | Depletion of ATP-Citrate Lyase (ATPCL) Affects Chromosome Integrity Without Altering Histone Acetylation in Drosophila Mitotic Cells |
| title_sort | depletion of atp citrate lyase atpcl affects chromosome integrity without altering histone acetylation in drosophila mitotic cells |
| topic | citrate lyase Drosophila chromosomes histone acetylation acetyl-CoA Drosophila |
| url | https://www.frontiersin.org/article/10.3389/fphys.2019.00383/full |
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