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The Drosophila Citrate Lyase Is Required for Cell Division during Spermatogenesis

Dipartimento di Biologia e Biotecnologie “C. Darwin”, SAPIENZA Università di Roma, P.le A. Moro 5, 00185 Rome, Italy
INFN-Laboratori Nazionali del Gran Sasso, I-67100 Assergi (L’Aquila), Italy
Istituto di Biologia e Patologia Molecolari (IBPM) del CNR, 00185 Rome, Italy
Istituto Pasteur, Fondazione Cenci Bolognetti, 00185 Rome, Italy
State Key Laboratory of Bio-Control, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(1), 206; (registering DOI)
Received: 23 December 2019 / Revised: 9 January 2020 / Accepted: 10 January 2020 / Published: 14 January 2020
The Drosophila melanogaster DmATPCL gene encodes for the human ATP Citrate Lyase (ACL) ortholog, a metabolic enzyme that from citrate generates glucose-derived Acetyl-CoA, which fuels central biochemical reactions such as the synthesis of fatty acids, cholesterol and acetylcholine, and the acetylation of proteins and histones. We had previously reported that, although loss of Drosophila ATPCL reduced levels of Acetyl-CoA, unlike its human counterpart, it does not affect global histone acetylation and gene expression, suggesting that its role in histone acetylation is either partially redundant in Drosophila or compensated by alternative pathways. Here, we describe that depletion of DmATPCL affects spindle organization, cytokinesis, and fusome assembly during male meiosis, revealing an unanticipated role for DmATPCL during spermatogenesis. We also show that DmATPCL mutant meiotic phenotype is in part caused by a reduction of fatty acids, but not of triglycerides or cholesterol, indicating that DmATPCL-derived Acetyl-CoA is predominantly devoted to the biosynthesis of fatty acids during spermatogenesis. Collectively, our results unveil for the first time an involvement for DmATPCL in the regulation of meiotic cell division, which is likely conserved in human cells. View Full-Text
Keywords: ACL; Drosophila; male meiosis; spermatogenesis ACL; Drosophila; male meiosis; spermatogenesis
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Di Giorgio, M.L.; Morciano, P.; Bucciarelli, E.; Porrazzo, A.; Cipressa, F.; Saraniero, S.; Manzi, D.; Rong, Y.S.; Cenci, G. The Drosophila Citrate Lyase Is Required for Cell Division during Spermatogenesis. Cells 2020, 9, 206.

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