Novel AARS2 gene mutations encoding mitochondrial alanyl-tRNA synthetase are important in the spectrum of different phenotypes expressed in the nervous system. Leukodystrophy and ovarian failure in females are common ...Novel AARS2 gene mutations encoding mitochondrial alanyl-tRNA synthetase are important in the spectrum of different phenotypes expressed in the nervous system. Leukodystrophy and ovarian failure in females are common phenotypes. Peripheral demyelination is not a recognized aspect of the AARS2 phenotype. A patient with preceding Lyme neuroborreliosis developed progressive leukodystrophy and peripheral demyelinating motor polyneuropathy. Serial magnetic resonance imaging showed progressive inflammatory demyelination extending to the corticospinal tracts. Treatment with a standard of care of antibiotics and immune-modulatory therapy employing intravenous immune globulin was employed. The contribution of neuroborreliosis is not well understood in the expression of the AARS2 phenotype.展开更多
A recent study by Li et al.[1]was published in Nature and proposed the crucial roles of lactylation in regulating innate immunity.Alanyl-tRNA synthetase 1(AARS1)and AARS2,the intracellular L-lactate sensors,were demon...A recent study by Li et al.[1]was published in Nature and proposed the crucial roles of lactylation in regulating innate immunity.Alanyl-tRNA synthetase 1(AARS1)and AARS2,the intracellular L-lactate sensors,were demonstrated to directly conjugate L-lactate to a lysine residue of substrate proteins.AARS2interacts with cGAS and mediates its lactylation,dampening cGAS-mediated innate antiviral response.展开更多
Chemoresistance remains the major barrier to cancer treatment.Metabolic and epigenetic reprogramming are involved in this process;however,the precise roles and mechanisms are largely unknown.Here,we report that lactat...Chemoresistance remains the major barrier to cancer treatment.Metabolic and epigenetic reprogramming are involved in this process;however,the precise roles and mechanisms are largely unknown.Here,we report that lactate-induced lactylation promotes chemoresistance to anthracyclines by regulating homologous recombination(HR)repair.Using the global lactylome,we revealed the landscape of differentially lactylated sites and proteins in cancer cells isolated from resistant and nonresistant tumors.Specifically,BLM,a crucial helicase in the HR repair process,is highly lactylated at Lys24 by AARS1 in response to chemotherapy.展开更多
文摘Novel AARS2 gene mutations encoding mitochondrial alanyl-tRNA synthetase are important in the spectrum of different phenotypes expressed in the nervous system. Leukodystrophy and ovarian failure in females are common phenotypes. Peripheral demyelination is not a recognized aspect of the AARS2 phenotype. A patient with preceding Lyme neuroborreliosis developed progressive leukodystrophy and peripheral demyelinating motor polyneuropathy. Serial magnetic resonance imaging showed progressive inflammatory demyelination extending to the corticospinal tracts. Treatment with a standard of care of antibiotics and immune-modulatory therapy employing intravenous immune globulin was employed. The contribution of neuroborreliosis is not well understood in the expression of the AARS2 phenotype.
基金supported by the National Natural Science Foundation of China(32270975,32070907,U24A20371,and T2321005)the National Key R&D Program of China(2023YFA1800200 and 2022YFA1105200)+3 种基金the National Science Fund for Distinguished Young Scholars(32125016)Suzhou Medical College basic frontier innovation cross project(YXY2303027)Suzhou Innovation and Entrepreneurship Leading Talent Program(ZXL2022505)the Priority Acadamic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘A recent study by Li et al.[1]was published in Nature and proposed the crucial roles of lactylation in regulating innate immunity.Alanyl-tRNA synthetase 1(AARS1)and AARS2,the intracellular L-lactate sensors,were demonstrated to directly conjugate L-lactate to a lysine residue of substrate proteins.AARS2interacts with cGAS and mediates its lactylation,dampening cGAS-mediated innate antiviral response.
基金supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2024ZD0525700 to T.L.)the National Natural Science Foundation of China(82403698 to X.L.)+5 种基金the Postdoctoral Fellowship Program of CPSF grant(GZC20233348 to X.L.)the National Natural Science Foundation of China grant(82472779 to X.G.)the National Natural Science Foundation of China grant(82372881 to W.H.)the Chongqing Natural Science Foundation(CSTB2024NSCQ-MSX1030 to X.L.)the Chongqing Medical Youth Top Talent Project(YXQN202431 to X.L.)the Qiande Excellent Young Talent Project(2025QDYQ-06 to X.L.).
文摘Chemoresistance remains the major barrier to cancer treatment.Metabolic and epigenetic reprogramming are involved in this process;however,the precise roles and mechanisms are largely unknown.Here,we report that lactate-induced lactylation promotes chemoresistance to anthracyclines by regulating homologous recombination(HR)repair.Using the global lactylome,we revealed the landscape of differentially lactylated sites and proteins in cancer cells isolated from resistant and nonresistant tumors.Specifically,BLM,a crucial helicase in the HR repair process,is highly lactylated at Lys24 by AARS1 in response to chemotherapy.
