Depletion of ATP-Citrate Lyase (ATPCL) Affects Chromosome Integrity Without Altering Histone Acetylation in Drosophila Mitotic Cells

Frontiers in Physiology

卷:10

Maria Laura Di Giorgio¹  Patrizia Morciano¹  Antonella Porrazzo²  Giovanni Cenci²  Valerio Licursi³  Rodolfo Negri⁴  Yikang Rong⁵ 

[1] Dipartimento di Biologia e Biotecnologie “Charles Darwin”, Sapienza – Università di Roma, Rome, Italy;

[2] Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy;

[3] Istituto di Analisi dei Sistemi ed Informatica “Antonio Ruberti”, Consiglio Nazionale delle Ricerche, Rome, Italy;

[4] Istituto di Biologia e Patologia Molecolari (IBPM) del CNR, Rome, Italy;

[5] School of Life Sciences, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou, China;

关键词: citrate lyase;    Drosophila chromosomes;    histone acetylation;    acetyl-CoA;    Drosophila;   

DOI  :  10.3389/fphys.2019.00383

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown