Chloride is the most abundant anion in living systems.Most natural or synthetic chloride anionophores function via hydrogen-bonding interactions.However,dynamic metal-anion coordination can also be an efficient way of...Chloride is the most abundant anion in living systems.Most natural or synthetic chloride anionophores function via hydrogen-bonding interactions.However,dynamic metal-anion coordination can also be an efficient way of transporting chloride across membranes.Here,we investigate anion transport by manganese(Ⅲ)meso-tetraphenylporphyrin chloride{[Mn(TPP)Cl],TPP=meso-tetraphenylporphyrin}complex that exhibits labile axial coordination.[Mn(TPP)Cl]showed high chloride transport activity in a bilayer vesicle model with an EC_(50) value of 4.42×10^(−3) mol%.In living cells,[Mn(TPP)Cl]induced rapid chloride influx and autophagy.The release of Ca^(2+)and adenosine 5′-triphosphate(ATP),as well as the relocation of calreticulin,revealed that[Mn(TPP)Cl]caused immunogenic cell death.Proteomic analysis indicated that[Mn(TPP)Cl]impaired several physiological processes,including DNA synthesis,transcription,mitochondrial respiration,RNA translation,and immune response.Our study suggests that dynamic metal-anion interactions across membranes might provide a practical strategy for the interference of chloride homeostasis.展开更多
基金supported by the National Natural Science Foundation of China(grant nos.22022707,21778078,21877057,91953117,21837006,and 21773314)the innovative team of Ministry of Education(grant no.IRT_17R111)+3 种基金the Fundamental Research Funds for the Central Universitiesthe Guangdong Natural Science Funds for Distinguished Young Scholar(2019B151502017)EPSRC(no.EP/P030572/1)Chinese Scholarship Council(to F.-X.W.).
文摘Chloride is the most abundant anion in living systems.Most natural or synthetic chloride anionophores function via hydrogen-bonding interactions.However,dynamic metal-anion coordination can also be an efficient way of transporting chloride across membranes.Here,we investigate anion transport by manganese(Ⅲ)meso-tetraphenylporphyrin chloride{[Mn(TPP)Cl],TPP=meso-tetraphenylporphyrin}complex that exhibits labile axial coordination.[Mn(TPP)Cl]showed high chloride transport activity in a bilayer vesicle model with an EC_(50) value of 4.42×10^(−3) mol%.In living cells,[Mn(TPP)Cl]induced rapid chloride influx and autophagy.The release of Ca^(2+)and adenosine 5′-triphosphate(ATP),as well as the relocation of calreticulin,revealed that[Mn(TPP)Cl]caused immunogenic cell death.Proteomic analysis indicated that[Mn(TPP)Cl]impaired several physiological processes,including DNA synthesis,transcription,mitochondrial respiration,RNA translation,and immune response.Our study suggests that dynamic metal-anion interactions across membranes might provide a practical strategy for the interference of chloride homeostasis.
