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.

The Drosophila Citrate Lyase Is Required for Cell Division during Spermatogenesis / Di Giorgio, Maria Laura; Morciano, Patrizia; Bucciarelli, Elisabetta; Porrazzo, Antonella; Cipressa, Francesca; Saraniero, Sara; Manzi, Diana; Rong, Yikang S; Cenci, Giovanni. - In: CELLS. - ISSN 2073-4409. - 9:1(2020), p. 206. [10.3390/cells9010206]

The Drosophila Citrate Lyase Is Required for Cell Division during Spermatogenesis

Di Giorgio, Maria Laura
Investigation
;
Morciano, Patrizia
Investigation
;
Bucciarelli, Elisabetta
Investigation
;
Porrazzo, Antonella
Investigation
;
Cipressa, Francesca
Investigation
;
Manzi, Diana
Methodology
;
Cenci, Giovanni
Writing – Review & Editing
2020

Abstract

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.
2020
ACL; Drosophila; male meiosis; spermatogenesis
01 Pubblicazione su rivista::01a Articolo in rivista
The Drosophila Citrate Lyase Is Required for Cell Division during Spermatogenesis / Di Giorgio, Maria Laura; Morciano, Patrizia; Bucciarelli, Elisabetta; Porrazzo, Antonella; Cipressa, Francesca; Saraniero, Sara; Manzi, Diana; Rong, Yikang S; Cenci, Giovanni. - In: CELLS. - ISSN 2073-4409. - 9:1(2020), p. 206. [10.3390/cells9010206]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1384362
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