The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species.Enzymatic shuttles,particularly adenyl...The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species.Enzymatic shuttles,particularly adenylate kinase(AK)and creatine kinase(CK),are pivotal in the efficient transfer of intracellular ATP,showing distinct tissue-and species-specificity.Here,the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups,of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates.Both AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male cohort.Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility.Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke(RS)of the axoneme.Examination of various human and mouse sperm samples with substructural damage,including the presence of multiple RS subunits,showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme.Using an ATP probe together with metabolomic analysis,it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme,and were concentrated at sites associated with energy consumption in the flagellum.These findings indicate a novel function for RS beyond its structural role,namely,the regulation of ATP transfer.In conclusion,the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.展开更多
Dear Editor,Male subfertility,a multifactorial disease affecting~7%of the global male population,is usually caused by abnormalities in sperm flagella.The flagella and motile cilia have similar“9+2”axonemes and are e...Dear Editor,Male subfertility,a multifactorial disease affecting~7%of the global male population,is usually caused by abnormalities in sperm flagella.The flagella and motile cilia have similar“9+2”axonemes and are evolutionarily conserved,being widely distributed in bacteria,archaea and eukaryotes1.Cilia defects also lead to primary ciliary dyskinesia(PCD),which affects approximately 1/10,000 individuals worldwide.展开更多
基金supported by National Key Research and Development Program of China(2022YFC2702702,2021YFC2700901)the National Natural Science Foundation of China(81971441,82171607,32000584)+3 种基金the University Outstanding Young Talents Support Program(gxyq2021174)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT310002)Anhui Provincial Natural Science Foundation(2208085Y31)the Natural Science Foundation of Jiangsu Province(BK20230004).
文摘The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species.Enzymatic shuttles,particularly adenylate kinase(AK)and creatine kinase(CK),are pivotal in the efficient transfer of intracellular ATP,showing distinct tissue-and species-specificity.Here,the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups,of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates.Both AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male cohort.Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility.Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke(RS)of the axoneme.Examination of various human and mouse sperm samples with substructural damage,including the presence of multiple RS subunits,showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme.Using an ATP probe together with metabolomic analysis,it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme,and were concentrated at sites associated with energy consumption in the flagellum.These findings indicate a novel function for RS beyond its structural role,namely,the regulation of ATP transfer.In conclusion,the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.
基金This work was supported by the National Key Research and Development Program of China(2022YFC2702702 to M.L.and 2022YFC2702604 to Y.T.)the National Natural Science Foundation of China(32270899 and 32070842 to M.L.,82101961,82171608,82201773 and 81971447 to Y.T.)+1 种基金the Natural Science Foundation of Jiangsu Province(BK20190081 to M.L.)Changsha Municipal Natural Science Foundation(kq2202493 to S.Y.).We sincerely appreciate Zhuang Xiao and Shuqin Zhao from State Key Laboratory of Reproductive Medicine,Nanjing Medical University,Chen Tan,Huan Zhang,Chaofeng Tu,Qinwei Zhou,Fei Meng,Qianjun Zhang,and Chunbo Xie from Reproductive and Genetic Hospital of CITIC-XIANGYA for their assistance in this study.
文摘Dear Editor,Male subfertility,a multifactorial disease affecting~7%of the global male population,is usually caused by abnormalities in sperm flagella.The flagella and motile cilia have similar“9+2”axonemes and are evolutionarily conserved,being widely distributed in bacteria,archaea and eukaryotes1.Cilia defects also lead to primary ciliary dyskinesia(PCD),which affects approximately 1/10,000 individuals worldwide.
