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      ATP synthase is required for male fertility and germ cell maturation in Drosophila testes

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          Abstract

          Germ cell maturation is essential for spermatogenesis and testis homeostasis. ATP synthase serves significant roles in energy storage in germ cell survival and is catalyzed by alterations in the mitochondrial membrane proton concentration. The intrinsic cellular mechanisms governing stem cell maturation remain largely unknown. In the present study, in vivo RNA interference (RNAi) screening of major ATP synthase subunits was performed, and the function of ATP synthase for male fertility and spermatogenesis in Drosophila was explored. A Upstream Activation Sequence/Gal4 transcription factor system was used to knock down gene expression in specific cell types, and immunofluorescence staining was conducted to assess the roles of ATP synthase subunits in Drosophila testes. It was identified that knockdown of ATP synthase resulted in male infertility and abnormal spermatogenesis in Drosophila testes. In addition, knockdown of the ATP synthase β subunit in germ cells resulted in defects in male infertility and germ cell maturation, while the hub and cyst cell populations were maintained. Other major ATP synthase subunits were also examined and similar phenotypes in Drosophila testes were identified. Taken together, the data from the present study revealed that ATP synthase serves important roles for male fertility during spermatogenesis by regulating germ cell maturation in Drosophila testes.

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          Most cited references38

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          The ATP synthase: the understood, the uncertain and the unknown.

          The ATP synthases are multiprotein complexes found in the energy-transducing membranes of bacteria, chloroplasts and mitochondria. They employ a transmembrane protonmotive force, Δp, as a source of energy to drive a mechanical rotary mechanism that leads to the chemical synthesis of ATP from ADP and Pi. Their overall architecture, organization and mechanistic principles are mostly well established, but other features are less well understood. For example, ATP synthases from bacteria, mitochondria and chloroplasts differ in the mechanisms of regulation of their activity, and the molecular bases of these different mechanisms and their physiological roles are only just beginning to emerge. Another crucial feature lacking a molecular description is how rotation driven by Δp is generated, and how rotation transmits energy into the catalytic sites of the enzyme to produce the stepping action during rotation. One surprising and incompletely explained deduction based on the symmetries of c-rings in the rotor of the enzyme is that the amount of energy required by the ATP synthase to make an ATP molecule does not have a universal value. ATP synthases from multicellular organisms require the least energy, whereas the energy required to make an ATP molecule in unicellular organisms and chloroplasts is higher, and a range of values has been calculated. Finally, evidence is growing for other roles of ATP synthases in the inner membranes of mitochondria. Here the enzymes form supermolecular complexes, possibly with specific lipids, and these complexes probably contribute to, or even determine, the formation of the cristae.
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            Structure of the yeast F1Fo-ATP synthase dimer and its role in shaping the mitochondrial cristae.

            We used electron cryotomography of mitochondrial membranes from wild-type and mutant Saccharomyces cerevisiae to investigate the structure and organization of ATP synthase dimers in situ. Subtomogram averaging of the dimers to 3.7 nm resolution revealed a V-shaped structure of twofold symmetry, with an angle of 86° between monomers. The central and peripheral stalks are well resolved. The monomers interact within the membrane at the base of the peripheral stalks. In wild-type mitochondria ATP synthase dimers are found in rows along the highly curved cristae ridges, and appear to be crucial for membrane morphology. Strains deficient in the dimer-specific subunits e and g or the first transmembrane helix of subunit 4 lack both dimers and lamellar cristae. Instead, cristae are either absent or balloon-shaped, with ATP synthase monomers distributed randomly in the membrane. Computer simulations indicate that isolated dimers induce a plastic deformation in the lipid bilayer, which is partially relieved by their side-by-side association. We propose that the assembly of ATP synthase dimer rows is driven by the reduction in the membrane elastic energy, rather than by direct protein contacts, and that the dimer rows enable the formation of highly curved ridges in mitochondrial cristae.
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              Male and female Drosophila germline stem cells: two versions of immortality.

              Drosophila male and female germline stem cells (GSCs) are sustained by niches and regulatory pathways whose common principles serve as models for understanding mammalian stem cells. Despite striking cellular and genetic similarities that suggest a common evolutionary origin, however, male and female GSCs also display important differences. Comparing these two stem cells and their niches in detail is likely to reveal how a common heritage has been adapted to the differing requirements of male and female gamete production.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                March 2019
                08 January 2019
                08 January 2019
                : 19
                : 3
                : 1561-1570
                Affiliations
                [1 ]Department of Gynecology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
                [2 ]Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
                [3 ]Reproductive Sciences Institute of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
                [4 ]Department of Urology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
                [5 ]Center for Reproduction and Genetics, Suzhou Municipal Hospital, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu 215002, P.R. China
                [6 ]Department of Clinical Pharmacy, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
                [7 ]Department of Clinical Medicine, China Medical University, Shenyang, Liaoning 110001, P.R. China
                [8 ]Department of Immunology, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
                Author notes
                Correspondence to: Dr Jun Yu or Professor Jie Fang, Department of Gynecology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu 212001, P.R. China, E-mail: yujun9117@ 123456126.com , E-mail: fangjie070@ 123456163.com
                [*]

                Contributed equally

                Article
                mmr-19-03-1561
                10.3892/mmr.2019.9834
                6390039
                30628672
                62812301-406c-4a07-b4cd-5816a8843920
                Copyright: © Yu et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 26 March 2018
                : 08 November 2018
                Categories
                Articles

                adenosine 5′-triphosphate synthase,male fertility,germ cell mature,drosophila,testis

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