2025年6月19日,上海交通大学医学院王戈林团队在Molecular Cell杂志上发表了题为“The NAMPT enzyme employs a switch that directly senses AMP/ATP and regulates cellular responses to energy stress”的研究论文。该研究首次揭示N...2025年6月19日,上海交通大学医学院王戈林团队在Molecular Cell杂志上发表了题为“The NAMPT enzyme employs a switch that directly senses AMP/ATP and regulates cellular responses to energy stress”的研究论文。该研究首次揭示NAD^(+)合成关键酶烟酰胺磷酸核糖转移酶(NAMPT)可直接感应AMP/ATP变化,兼具“能量传感器”与“NAD^(+)合成控制开关”的双重功能,协调ATP和NAD^(+)2条基本能量代谢通路,为缺血性脑卒中等疾病的治疗提供了潜在药物靶点。展开更多
BACKGROUND Glycolysis provides growth advantages and leads to drug resistance in colorectal cancer(CRC)cells.SIRT1,an NAD+-dependent deacetylase,regulates various cellular processes,and its upregulation results in ant...BACKGROUND Glycolysis provides growth advantages and leads to drug resistance in colorectal cancer(CRC)cells.SIRT1,an NAD+-dependent deacetylase,regulates various cellular processes,and its upregulation results in antitumor effects.This study investigated the role of SIRT1 in metabolic reprogramming and oxaliplatin resistance in CRC cells.AIM To investigate the role of SIRT1 in metabolic reprogramming and overcoming oxaliplatin resistance in CRC cells.METHODS We performed transcriptome sequencing of human CRC parental cells and oxaliplatin-resistant cells to identify differentially expressed genes.Key regulators were identified via the LINCS database.NAD+levels were measured by flow cytometry,and the effects of SIRT1 on oxaliplatin sensitivity were assessed by MTS assays,colony formation assays,and xenograft models.Glycolytic function was measured using Western blot and Seahorse assays.RESULTS Salermide,a SIRT1 inhibitor,was identified as a candidate compound that enhances oxaliplatin resistance.In oxaliplatin-resistant cells,SIRT1 was downregulated,whereasγH2AX and PARP were upregulated.PARP activation led to NAD+depletion and SIRT1 inhibition,which were reversed by PARP inhibitor treatment.The increase in SIRT1 expression overcame oxaliplatin resistance,and while SIRT1 inhibition increased glycolysis,the increase in SIRT1 inhibited glycolysis in resistant CRC cells,which was charac-terized by reduced expression of the glycolytic enzymes PKM2 and LDHA,as well as a decreased extracellular acidification rate.The PKM2 inhibitor shikonin inhibited glycolysis and reversed oxaliplatin resistance induced by SIRT1 inhibition.CONCLUSION SIRT1 expression is reduced in oxaliplatin-resistant CRC cells due to PARP activation,which in turn increases glycolysis.Restoring SIRT1 expression reverses oxaliplatin resistance in CRC cells,offering a promising therapeutic strategy to overcome drug resistance.展开更多
Mitochondria are semi-autonomous organelles present in eukaryotic cells,containing their own genome and transcriptional machinery.However,their functions are intricately linked to proteins encoded by the nuclear genom...Mitochondria are semi-autonomous organelles present in eukaryotic cells,containing their own genome and transcriptional machinery.However,their functions are intricately linked to proteins encoded by the nuclear genome.Mitochondrial transcription termination factors(mTERFs)are nucleic acid-binding proteins involved in RNA splicing and transcription termination within plant mitochondria and chloroplasts.Despite their recognized importance,the specific roles of mTERF proteins in maize remain largely unexplored.Here,we clone and functionally characterize the maize mTERF18 gene.Our findings reveal that mTERF18 mutations lead to severely undifferentiated embryos,resulting in abortive phenotypes.Early kernel exhibits abnormal basal endosperm transfer layer and a significant reduction in both starch and protein accumulation in mterf18.We identify the mTERF18 gene through mapping-based cloning and validate this gene through allelic tests.mTERF18 is widely expressed across various maize tissues and encodes a highly conserved mitochondrial protein.Transcriptome data reveal that mTERF18 mutations disrupt transcriptional termination of the nad6 gene,leading to undetectable levels of Nad6 protein and reduced complex I assembly and activity.Furthermore,transmission electron microscopy observation of mterf18 endosperm uncover severe mitochondrial defects.Collectively,these findings highlight the critical role of mTERF18 in mitochondrial gene transcription termination and its pivotal impact on maize kernel development.展开更多
2025年6月3日,北京大学药学院天然药物及仿生药物全国重点实验室谢海燕教授团队与南开大学庞代文教授合作,在Nature Biomedical Engineering杂志发表了题为“NAD+biosynthesis and mitochondrial repair in acute kidney injury via ult...2025年6月3日,北京大学药学院天然药物及仿生药物全国重点实验室谢海燕教授团队与南开大学庞代文教授合作,在Nature Biomedical Engineering杂志发表了题为“NAD+biosynthesis and mitochondrial repair in acute kidney injury via ultrasound-responsive thylakoid-integrating liposomes”的研究论文,该研究开发了一种可超声驱动的新型仿生脂质类囊体系统,通过重塑肾细胞内的NAD+能量代谢过程,高效恢复胞内能量供给和抗氧化能力,治疗急性肾损伤(AKI)。展开更多
文摘2025年6月19日,上海交通大学医学院王戈林团队在Molecular Cell杂志上发表了题为“The NAMPT enzyme employs a switch that directly senses AMP/ATP and regulates cellular responses to energy stress”的研究论文。该研究首次揭示NAD^(+)合成关键酶烟酰胺磷酸核糖转移酶(NAMPT)可直接感应AMP/ATP变化,兼具“能量传感器”与“NAD^(+)合成控制开关”的双重功能,协调ATP和NAD^(+)2条基本能量代谢通路,为缺血性脑卒中等疾病的治疗提供了潜在药物靶点。
基金Supported by the National Natural Science Foundation of China,No.82072756Beijing Xisike Clinical Oncology Research Foundation,No.Y-HR2019-0285.
文摘BACKGROUND Glycolysis provides growth advantages and leads to drug resistance in colorectal cancer(CRC)cells.SIRT1,an NAD+-dependent deacetylase,regulates various cellular processes,and its upregulation results in antitumor effects.This study investigated the role of SIRT1 in metabolic reprogramming and oxaliplatin resistance in CRC cells.AIM To investigate the role of SIRT1 in metabolic reprogramming and overcoming oxaliplatin resistance in CRC cells.METHODS We performed transcriptome sequencing of human CRC parental cells and oxaliplatin-resistant cells to identify differentially expressed genes.Key regulators were identified via the LINCS database.NAD+levels were measured by flow cytometry,and the effects of SIRT1 on oxaliplatin sensitivity were assessed by MTS assays,colony formation assays,and xenograft models.Glycolytic function was measured using Western blot and Seahorse assays.RESULTS Salermide,a SIRT1 inhibitor,was identified as a candidate compound that enhances oxaliplatin resistance.In oxaliplatin-resistant cells,SIRT1 was downregulated,whereasγH2AX and PARP were upregulated.PARP activation led to NAD+depletion and SIRT1 inhibition,which were reversed by PARP inhibitor treatment.The increase in SIRT1 expression overcame oxaliplatin resistance,and while SIRT1 inhibition increased glycolysis,the increase in SIRT1 inhibited glycolysis in resistant CRC cells,which was charac-terized by reduced expression of the glycolytic enzymes PKM2 and LDHA,as well as a decreased extracellular acidification rate.The PKM2 inhibitor shikonin inhibited glycolysis and reversed oxaliplatin resistance induced by SIRT1 inhibition.CONCLUSION SIRT1 expression is reduced in oxaliplatin-resistant CRC cells due to PARP activation,which in turn increases glycolysis.Restoring SIRT1 expression reverses oxaliplatin resistance in CRC cells,offering a promising therapeutic strategy to overcome drug resistance.
基金supported by the National Key Research and Development Program of China(2021YFF1000304)the National Natural Science Foundation of China(32222060)Anhui Agricultural University(RC422404)to J.Y.
文摘Mitochondria are semi-autonomous organelles present in eukaryotic cells,containing their own genome and transcriptional machinery.However,their functions are intricately linked to proteins encoded by the nuclear genome.Mitochondrial transcription termination factors(mTERFs)are nucleic acid-binding proteins involved in RNA splicing and transcription termination within plant mitochondria and chloroplasts.Despite their recognized importance,the specific roles of mTERF proteins in maize remain largely unexplored.Here,we clone and functionally characterize the maize mTERF18 gene.Our findings reveal that mTERF18 mutations lead to severely undifferentiated embryos,resulting in abortive phenotypes.Early kernel exhibits abnormal basal endosperm transfer layer and a significant reduction in both starch and protein accumulation in mterf18.We identify the mTERF18 gene through mapping-based cloning and validate this gene through allelic tests.mTERF18 is widely expressed across various maize tissues and encodes a highly conserved mitochondrial protein.Transcriptome data reveal that mTERF18 mutations disrupt transcriptional termination of the nad6 gene,leading to undetectable levels of Nad6 protein and reduced complex I assembly and activity.Furthermore,transmission electron microscopy observation of mterf18 endosperm uncover severe mitochondrial defects.Collectively,these findings highlight the critical role of mTERF18 in mitochondrial gene transcription termination and its pivotal impact on maize kernel development.
文摘2025年6月3日,北京大学药学院天然药物及仿生药物全国重点实验室谢海燕教授团队与南开大学庞代文教授合作,在Nature Biomedical Engineering杂志发表了题为“NAD+biosynthesis and mitochondrial repair in acute kidney injury via ultrasound-responsive thylakoid-integrating liposomes”的研究论文,该研究开发了一种可超声驱动的新型仿生脂质类囊体系统,通过重塑肾细胞内的NAD+能量代谢过程,高效恢复胞内能量供给和抗氧化能力,治疗急性肾损伤(AKI)。
