Pub Date : 2024-06-04DOI: 10.1038/s41422-024-00984-7
Changyao Li, Heng Liu, Jingru Li, Xinheng He, Haoran Zhu, Wei Fu, H. Eric Xu
{"title":"Molecular basis of ligand recognition and activation of the human succinate receptor SUCR1","authors":"Changyao Li, Heng Liu, Jingru Li, Xinheng He, Haoran Zhu, Wei Fu, H. Eric Xu","doi":"10.1038/s41422-024-00984-7","DOIUrl":"10.1038/s41422-024-00984-7","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1038/s41422-024-00983-8
Haopeng Wang, Shizhen Qiu, Mohamad Mohty
{"title":"All-in-one Hangzhou Protocol: killing four birds with one stone","authors":"Haopeng Wang, Shizhen Qiu, Mohamad Mohty","doi":"10.1038/s41422-024-00983-8","DOIUrl":"10.1038/s41422-024-00983-8","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-00983-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141182864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bidirectional transcription of mammalian mitochondrial DNA generates overlapping transcripts that are capable of forming double-stranded RNA (dsRNA) structures. Release of mitochondrial dsRNA into the cytosol activates the dsRNA-sensing immune signaling, which is a defense mechanism against microbial and viral attack and possibly cancer, but could cause autoimmune diseases when unchecked. A better understanding of the process is vital in therapeutic application of this defense mechanism and treatment of cognate human diseases. In addition to exporting dsRNAs, mitochondria also export and import a variety of non-coding RNAs. However, little is known about how these RNAs are transported across mitochondrial membranes. Here we provide direct evidence showing that adenine nucleotide translocase-2 (ANT2) functions as a mammalian RNA translocon in the mitochondrial inner membrane, independent of its ADP/ATP translocase activity. We also show that mitochondrial dsRNA efflux through ANT2 triggers innate immunity. Inhibiting this process alleviates inflammation in vivo, providing a potential therapeutic approach for treating autoimmune diseases.
{"title":"ANT2 functions as a translocon for mitochondrial cross-membrane translocation of RNAs","authors":"Pengcheng Wang, Lixiao Zhang, Siyi Chen, Renjian Li, Peipei Liu, Xiang Li, Hongdi Luo, Yujia Huo, Zhirong Zhang, Yiqi Cai, Xu Liu, Jinliang Huang, Guangkeng Zhou, Zhe Sun, Shanwei Ding, Jiahao Shi, Zizhuo Zhou, Ruoxi Yuan, Liang Liu, Sipeng Wu, Geng Wang","doi":"10.1038/s41422-024-00978-5","DOIUrl":"10.1038/s41422-024-00978-5","url":null,"abstract":"Bidirectional transcription of mammalian mitochondrial DNA generates overlapping transcripts that are capable of forming double-stranded RNA (dsRNA) structures. Release of mitochondrial dsRNA into the cytosol activates the dsRNA-sensing immune signaling, which is a defense mechanism against microbial and viral attack and possibly cancer, but could cause autoimmune diseases when unchecked. A better understanding of the process is vital in therapeutic application of this defense mechanism and treatment of cognate human diseases. In addition to exporting dsRNAs, mitochondria also export and import a variety of non-coding RNAs. However, little is known about how these RNAs are transported across mitochondrial membranes. Here we provide direct evidence showing that adenine nucleotide translocase-2 (ANT2) functions as a mammalian RNA translocon in the mitochondrial inner membrane, independent of its ADP/ATP translocase activity. We also show that mitochondrial dsRNA efflux through ANT2 triggers innate immunity. Inhibiting this process alleviates inflammation in vivo, providing a potential therapeutic approach for treating autoimmune diseases.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-27DOI: 10.1038/s41422-024-00982-9
Hiroyuki Kato, Nabeel Bardeesy
{"title":"Illuminating the path to pancreatic cancer","authors":"Hiroyuki Kato, Nabeel Bardeesy","doi":"10.1038/s41422-024-00982-9","DOIUrl":"10.1038/s41422-024-00982-9","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-00982-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-27DOI: 10.1038/s41422-024-00977-6
Carlos López-Otín, Andrea B. Maier, Guido Kroemer
{"title":"Gerogenes and gerosuppression: the pillars of precision geromedicine","authors":"Carlos López-Otín, Andrea B. Maier, Guido Kroemer","doi":"10.1038/s41422-024-00977-6","DOIUrl":"10.1038/s41422-024-00977-6","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-23DOI: 10.1038/s41422-024-00979-4
Pavel Hanč, Ulrich H. von Andrian
{"title":"No pain, no gain — how nociceptors orchestrate tissue repair","authors":"Pavel Hanč, Ulrich H. von Andrian","doi":"10.1038/s41422-024-00979-4","DOIUrl":"10.1038/s41422-024-00979-4","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-00979-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-22DOI: 10.1038/s41422-024-00971-y
Tae-Yoon Park, Jeha Jeon, Young Cha, Kwang-Soo Kim
Parkinson’s disease (PD) stands as the second most common neurodegenerative disorder after Alzheimer’s disease, and its prevalence continues to rise with the aging global population. Central to the pathophysiology of PD is the specific degeneration of midbrain dopamine neurons (mDANs) in the substantia nigra. Consequently, cell replacement therapy (CRT) has emerged as a promising treatment approach, initially supported by various open-label clinical studies employing fetal ventral mesencephalic (fVM) cells. Despite the initial favorable results, fVM cell therapy has intrinsic and logistical limitations that hinder its transition to a standard treatment for PD. Recent efforts in the field of cell therapy have shifted its focus towards the utilization of human pluripotent stem cells, including human embryonic stem cells and induced pluripotent stem cells, to surmount existing challenges. However, regardless of the transplantable cell sources (e.g., xenogeneic, allogeneic, or autologous), the poor and variable survival of implanted dopamine cells remains a major obstacle. Emerging evidence highlights the pivotal role of host immune responses following transplantation in influencing the survival of implanted mDANs, underscoring an important area for further research. In this comprehensive review, building upon insights derived from previous fVM transplantation studies, we delve into the functional ramifications of host immune responses on the survival and efficacy of grafted dopamine cells. Furthermore, we explore potential strategic approaches to modulate the host immune response, ultimately aiming for optimal outcomes in future clinical applications of CRT for PD.
{"title":"Past, present, and future of cell replacement therapy for parkinson’s disease: a novel emphasis on host immune responses","authors":"Tae-Yoon Park, Jeha Jeon, Young Cha, Kwang-Soo Kim","doi":"10.1038/s41422-024-00971-y","DOIUrl":"10.1038/s41422-024-00971-y","url":null,"abstract":"Parkinson’s disease (PD) stands as the second most common neurodegenerative disorder after Alzheimer’s disease, and its prevalence continues to rise with the aging global population. Central to the pathophysiology of PD is the specific degeneration of midbrain dopamine neurons (mDANs) in the substantia nigra. Consequently, cell replacement therapy (CRT) has emerged as a promising treatment approach, initially supported by various open-label clinical studies employing fetal ventral mesencephalic (fVM) cells. Despite the initial favorable results, fVM cell therapy has intrinsic and logistical limitations that hinder its transition to a standard treatment for PD. Recent efforts in the field of cell therapy have shifted its focus towards the utilization of human pluripotent stem cells, including human embryonic stem cells and induced pluripotent stem cells, to surmount existing challenges. However, regardless of the transplantable cell sources (e.g., xenogeneic, allogeneic, or autologous), the poor and variable survival of implanted dopamine cells remains a major obstacle. Emerging evidence highlights the pivotal role of host immune responses following transplantation in influencing the survival of implanted mDANs, underscoring an important area for further research. In this comprehensive review, building upon insights derived from previous fVM transplantation studies, we delve into the functional ramifications of host immune responses on the survival and efficacy of grafted dopamine cells. Furthermore, we explore potential strategic approaches to modulate the host immune response, ultimately aiming for optimal outcomes in future clinical applications of CRT for PD.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-22DOI: 10.1038/s41422-024-00976-7
Jang Hyun Park, Jenolyn F. Alexander, Leon C. D. Smyth, Jonathan Kipnis
{"title":"DALT: the brain’s border patrol","authors":"Jang Hyun Park, Jenolyn F. Alexander, Leon C. D. Smyth, Jonathan Kipnis","doi":"10.1038/s41422-024-00976-7","DOIUrl":"10.1038/s41422-024-00976-7","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-00976-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular activation and G protein coupling selectivity of human succinate receptor SUCR1","authors":"Tianxin Wang, Wenqin Tang, Xiaolei Zhu, Zhenyu Lv, Jiayan Chen, Yongze Li, Xiaoyu Sun, Haoyu Lv, Quanchang Gu, Fahui Li, Jiangyun Wang","doi":"10.1038/s41422-024-00968-7","DOIUrl":"10.1038/s41422-024-00968-7","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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