Interorganelle contacts and communications are increasingly recognized to play a vital role in cellular function and homeostasis.In particular,the mitochondria–endoplasmic reticulum(ER)membrane contact site(MAM)is kn...Interorganelle contacts and communications are increasingly recognized to play a vital role in cellular function and homeostasis.In particular,the mitochondria–endoplasmic reticulum(ER)membrane contact site(MAM)is known to regulate ion and lipid transfer,as well as signaling and organelle dynamics.However,the regulatory mechanisms of MAM formation and their function are still elusive.Here,we identify mitochondrial Lon protease(LonP1),a highly conserved mitochondrial matrix protease,as a new MAM tethering protein.The removal of LonP1 substantially reduces MAM formation and causes mitochondrial fragmentation.Furthermore,deletion of LonP1 in the cardiomyocytes of mouse heart impairs MAM integrity and mitochondrial fusion and activates the unfolded protein response within the ER(UPR^(ER)).Consequently,cardiac-specific LonP1 deficiency causes aberrant metabolic reprogramming and pathological heart remodeling.These findings demonstrate that LonP1 is a novel MAM-localized protein orchestrating MAM integrity,mitochondrial dynamics,and UPR^(ER),offering exciting new insights into the potential therapeutic strategy for heart failure.展开更多
OBJECTIVE： To review the efficacy of Tianshu capsule in the treatment of migraine. METHODS： Retrieving papers from Pubmed, cochrane central register of controlled trials （CENTRAL）, Weipu database （VIP）, China bi...OBJECTIVE： To review the efficacy of Tianshu capsule in the treatment of migraine. METHODS： Retrieving papers from Pubmed, cochrane central register of controlled trials （CENTRAL）, Weipu database （VIP）, China biology medicine （CBM）, China national knowledge infrastructure （CNKI）, and Wanfang Data. Two reviewers retrieved and extracted the information indepen- dently. Retrieval time scale is up to August 2012.Software Review Manager 5.1 was used for analysis RESULTS： A total of 10 studies including 937 mi- graine patients. The merged data shows Tianshu capsule had a higher effective rate in treating mi- graine, and there is no significant heterogeneity between Tianshu capsule group and control group （x2=6.33, dr-=9, P=0.71, F=0%）, OR=4.18 [95%0 （2.93,5.95）]. Tianshu capsule alone compared to conventional therapy also showed advantages, and there was low heterogeneity （X2=4.53, dr=3, P=0.21, 12 = 34%）, OR=3.95 [95% CI （2.32, 6.72）]. Meta-analysis results show that clinical efficacy of Tianshu capsule was better than that of the control group in the treatment of migraine and there was a signifi- cant difference （P〈0.000 01）. CONCLUSION： Tianshu capsule had better efficacy in the treatment of migraine with fewer adverse effects.展开更多
基金grants from National Natural Science Foundation of China(91954101,31771534,31570772,and 31070710 to B.L.and 81774022 to L.J.)National Basic Research Program of China(973 Program,2013CB531702 to B.L.and 2013CB531704 to G.Y.)the Scientific Research Foundation of University of South China(211RJC002 to B.L.).
文摘Interorganelle contacts and communications are increasingly recognized to play a vital role in cellular function and homeostasis.In particular,the mitochondria–endoplasmic reticulum(ER)membrane contact site(MAM)is known to regulate ion and lipid transfer,as well as signaling and organelle dynamics.However,the regulatory mechanisms of MAM formation and their function are still elusive.Here,we identify mitochondrial Lon protease(LonP1),a highly conserved mitochondrial matrix protease,as a new MAM tethering protein.The removal of LonP1 substantially reduces MAM formation and causes mitochondrial fragmentation.Furthermore,deletion of LonP1 in the cardiomyocytes of mouse heart impairs MAM integrity and mitochondrial fusion and activates the unfolded protein response within the ER(UPR^(ER)).Consequently,cardiac-specific LonP1 deficiency causes aberrant metabolic reprogramming and pathological heart remodeling.These findings demonstrate that LonP1 is a novel MAM-localized protein orchestrating MAM integrity,mitochondrial dynamics,and UPR^(ER),offering exciting new insights into the potential therapeutic strategy for heart failure.
基金Supported by Liaoning province science and technology plan projects : Traditional Chinese Medicine Efficacy Evaluation Key Technology Research (No. 2010225034)Ministry Of Science And Welfare Industry Research And Special (No.200807061)
文摘OBJECTIVE： To review the efficacy of Tianshu capsule in the treatment of migraine. METHODS： Retrieving papers from Pubmed, cochrane central register of controlled trials （CENTRAL）, Weipu database （VIP）, China biology medicine （CBM）, China national knowledge infrastructure （CNKI）, and Wanfang Data. Two reviewers retrieved and extracted the information indepen- dently. Retrieval time scale is up to August 2012.Software Review Manager 5.1 was used for analysis RESULTS： A total of 10 studies including 937 mi- graine patients. The merged data shows Tianshu capsule had a higher effective rate in treating mi- graine, and there is no significant heterogeneity between Tianshu capsule group and control group （x2=6.33, dr-=9, P=0.71, F=0%）, OR=4.18 [95%0 （2.93,5.95）]. Tianshu capsule alone compared to conventional therapy also showed advantages, and there was low heterogeneity （X2=4.53, dr=3, P=0.21, 12 = 34%）, OR=3.95 [95% CI （2.32, 6.72）]. Meta-analysis results show that clinical efficacy of Tianshu capsule was better than that of the control group in the treatment of migraine and there was a signifi- cant difference （P〈0.000 01）. CONCLUSION： Tianshu capsule had better efficacy in the treatment of migraine with fewer adverse effects.
