Mitochondrial DNA(mt DNA)mutations have been implicated in a broad range of disorders which severely affect human health(Wallace,1999).Some drugs have been developed to slow down pathological changes of mitochondrial ...Mitochondrial DNA(mt DNA)mutations have been implicated in a broad range of disorders which severely affect human health(Wallace,1999).Some drugs have been developed to slow down pathological changes of mitochondrial disorders.However,there is no effective treatment for patients with mt DNA mutations.mt DNA is less protected and has fewer repair mechanisms than nuclear DNA(n DNA).Such a reality results in a much higher展开更多
Mitochondria,double-membrane organelles,are known to participate in a variety of metabolic and signal transduction pathways.The intermembrane space(IMS)of mitochondria is proposed to subject to multiple damages emanat...Mitochondria,double-membrane organelles,are known to participate in a variety of metabolic and signal transduction pathways.The intermembrane space(IMS)of mitochondria is proposed to subject to multiple damages emanating from the respiratory chain.The optic atrophy 1(OPA1),an important protein for mitochondrial fusion,is cleaved into soluble short-form(S-OPA1)under stresses.Here we report that S-OPA1 could function as a molecular chaperone in IMS.We purified the S-OPA1(amino acid sequence after OPA1 isoform 5 S1 site)protein and showed it protected substrate proteins from thermally and chemically induced aggregation and strengthened the thermotolerance of Escherichia coli(E.coli).We also showed that S-OPA1 conferred thermotolerance on IMS proteins,e.g.,neurolysin.The chaperone activity of S-OPA1 may be required for maintaining IMS homeostasis in mitochondria.展开更多
基金supported by the National Basic Research Program of China (2013CB967403, 2012CB721105)the ‘‘Strategic Priority Research Program’’ of the Chinese Academy of Sciences (XDA01020108)+7 种基金the National High-tech R&D Program (2012AA02A708)the National Natural Science Foundation projects of China (31271527, 81570520)Guangzhou Science and Technology Program (2014Y2-00161)Guangdong Natural Science Foundation for Distinguished Young Scientists (S20120011368)Guangdong Province Science and Technology Innovation Young Talents Program (2014TQ01R559)Guangdong Province Science and Technology Program (2015A020212031)the Ph D Start-up Fund of Natural Science Foundation of Guangdong Province (2014A030310071)the ‘‘One Hundred Talents’’ Project for Prof. Xingguo Liu from the Chinese Academy of Sciences
文摘Mitochondrial DNA(mt DNA)mutations have been implicated in a broad range of disorders which severely affect human health(Wallace,1999).Some drugs have been developed to slow down pathological changes of mitochondrial disorders.However,there is no effective treatment for patients with mt DNA mutations.mt DNA is less protected and has fewer repair mechanisms than nuclear DNA(n DNA).Such a reality results in a much higher
基金the National Key Re-search and Development Program of China(2017YFA0106300)the Stra-tegic Priority Research Program of the Chinese Academy of Sciences(XDA16030505)+6 种基金the National Key Research and Development Program of China(2017YFA0102900,2019YFA09004500,2017YFC1001602,2016YFA0100300,2018YFA0107100)the National Natural Science Foundation of China(32025010,31801168,31900614,31970709,81901275,32070729)the Key Research Program of Frontier Sciences,CAS(QYZDB-SSW-SMC001)International Cooperation Program,CAS(154144KYSB20200006)Guangdong Province Science and Technol-ogy Program(2020B1212060052,2018A030313825,2018GZR110103002,2020A1515011200,2020A1515010919,2020A1515011410,2021A1515012513)Guangzhou Science and Technology Program(201807010067,202002030277,202102021250,202102020827,202102080066)CAS Youth Innovation Promotion Association.
文摘Mitochondria,double-membrane organelles,are known to participate in a variety of metabolic and signal transduction pathways.The intermembrane space(IMS)of mitochondria is proposed to subject to multiple damages emanating from the respiratory chain.The optic atrophy 1(OPA1),an important protein for mitochondrial fusion,is cleaved into soluble short-form(S-OPA1)under stresses.Here we report that S-OPA1 could function as a molecular chaperone in IMS.We purified the S-OPA1(amino acid sequence after OPA1 isoform 5 S1 site)protein and showed it protected substrate proteins from thermally and chemically induced aggregation and strengthened the thermotolerance of Escherichia coli(E.coli).We also showed that S-OPA1 conferred thermotolerance on IMS proteins,e.g.,neurolysin.The chaperone activity of S-OPA1 may be required for maintaining IMS homeostasis in mitochondria.