Industrial activities such as smelting emissions,mineral combustion and industrial wastewater discharge might lead to copper pollution in the environment.This kind of copper pollution has harmful effects on aquatic o ...Industrial activities such as smelting emissions,mineral combustion and industrial wastewater discharge might lead to copper pollution in the environment.This kind of copper pollution has harmful effects on aquatic o rganisms,plants and animals through direct or indirect exposure.However,the current understanding of the toxicity of copper is rather limited.Copper overload can perturb intracellular homeostasis and induce oxidative stress and e ven cell death.Recently,cuproptosis has been identified as a copper-dependent form of cell death induced by o xidative stress in mitochondria.We uncover here that zinc transporter 1(ZNT1)is an important regulator involved in cuproptosis.Firstly,we established the copper overload-induced cell death model with the overexpression of copper importer SLC31A1 in HeLa cells.Using this model,we conducted unbiased genome-wide CRISPR-Cas9 screens in cells treated with copper.Our results revealed a significant enrichment of ZNT1 gene in both library A and library B plasmids.Knocking out of ZNT1 in HeLa cells notably prevented cuproptosis.Subsequent knockout of metal transcription factor 1(MTF1)in ZNT1-deficient cells nearly abolished their ability to resist copper-induced cell death.However,overexpression of metallothionein 1X(MT1X)in the double-knockout cells could p artially restored the resistance to cuproptosis by loss of MTF1.Mechanistically,knockout of ZNT1 could promote MT1X expression by activating MTF1.As a consequence,the interaction between MT1X and copper was e nhanced,reducing the flow of copper into mitochondria and eliminating mitochondria damage.Taken together,this study reveals the important role of ZNT1 in cuproptosis and shows MTF1-MT1X axis mediated resistance to c uproptosis.Moreover,our study will help to understand the regulatory mechanism of cellular and systemic copper homeostasis under copper overload,and present insights into novel treatments for damages caused by both genetic copper overload diseases and environmental copper contamination.展开更多
Mountain streams act as conveyors of sediments within the river continuum,where the physical transport of sediments between river reaches through the catchment or between individual parts(e.g.,between hillslopes and c...Mountain streams act as conveyors of sediments within the river continuum,where the physical transport of sediments between river reaches through the catchment or between individual parts(e.g.,between hillslopes and channels)of the catchment is assumed.This study focused on sediment connectivity analysis in the SlavíčRiver catchment in the MoravskoslezskéBeskydy Mts in the eastern part of the Czech Republic.The connectivity index and connectivity index target modelling were combined with an analysis of anthropogenic interventions.Additionally,field mapping,grain size of bed sediments and stream power analysis were used to obtain information about connectivity in the catchment.Based on the analysis and obtained results,terrain topography is the current main driving factor affecting the connectivity of sediment movement in the SlavíčRiver catchment.However,the modelling provided valuable information about high sediment connectivity despite different recent land use conditions(highly forested area of the catchment)than those in historical times from the 16th to 19th centuries when the SlavíčRiver catchment was highly deforested and sediment connectivity was probably higher.The analysis of anthropogenic interventions,field mapping,grain size of bed sediments and stream power analysis revealed more deceleration of sediment movement through the catchment,decreased sediment connectivity with bed erosion,and gradual river channel process transformation in some reaches.Field mapping has identified various natural formations and human-induced changes impacting the longitudinal and lateral connectivity in the SlavíčRiver.For instance,embankments along 48%of the river's length,both on the right and left banks,significantly hinder lateral sediment supply to the channel.Stream power index analysis indicates increased energy levels in the flowing water in the river's upper reaches(up to 404.8 W m^(-2)).This high energy is also observed in certain downstream sections(up to 337.6 W m^(-2)),where it is influenced by human activities.These conditions lead to intensified erosion processes,playing a crucial role in sediment connectivity.Similar observations were described in recent studies that pointed out the long-term human interventions on many streams draining European mountains,where a decrease in sediment connectivity in these streams is linked with sediment deficits and the transformation of processes forming channels.展开更多
文摘Industrial activities such as smelting emissions,mineral combustion and industrial wastewater discharge might lead to copper pollution in the environment.This kind of copper pollution has harmful effects on aquatic o rganisms,plants and animals through direct or indirect exposure.However,the current understanding of the toxicity of copper is rather limited.Copper overload can perturb intracellular homeostasis and induce oxidative stress and e ven cell death.Recently,cuproptosis has been identified as a copper-dependent form of cell death induced by o xidative stress in mitochondria.We uncover here that zinc transporter 1(ZNT1)is an important regulator involved in cuproptosis.Firstly,we established the copper overload-induced cell death model with the overexpression of copper importer SLC31A1 in HeLa cells.Using this model,we conducted unbiased genome-wide CRISPR-Cas9 screens in cells treated with copper.Our results revealed a significant enrichment of ZNT1 gene in both library A and library B plasmids.Knocking out of ZNT1 in HeLa cells notably prevented cuproptosis.Subsequent knockout of metal transcription factor 1(MTF1)in ZNT1-deficient cells nearly abolished their ability to resist copper-induced cell death.However,overexpression of metallothionein 1X(MT1X)in the double-knockout cells could p artially restored the resistance to cuproptosis by loss of MTF1.Mechanistically,knockout of ZNT1 could promote MT1X expression by activating MTF1.As a consequence,the interaction between MT1X and copper was e nhanced,reducing the flow of copper into mitochondria and eliminating mitochondria damage.Taken together,this study reveals the important role of ZNT1 in cuproptosis and shows MTF1-MT1X axis mediated resistance to c uproptosis.Moreover,our study will help to understand the regulatory mechanism of cellular and systemic copper homeostasis under copper overload,and present insights into novel treatments for damages caused by both genetic copper overload diseases and environmental copper contamination.
基金supported by an internal grant of the University of Ostrava[SGS10/PřF/2021-Specificity of fluvial landscape in the context of historical and future changes].
文摘Mountain streams act as conveyors of sediments within the river continuum,where the physical transport of sediments between river reaches through the catchment or between individual parts(e.g.,between hillslopes and channels)of the catchment is assumed.This study focused on sediment connectivity analysis in the SlavíčRiver catchment in the MoravskoslezskéBeskydy Mts in the eastern part of the Czech Republic.The connectivity index and connectivity index target modelling were combined with an analysis of anthropogenic interventions.Additionally,field mapping,grain size of bed sediments and stream power analysis were used to obtain information about connectivity in the catchment.Based on the analysis and obtained results,terrain topography is the current main driving factor affecting the connectivity of sediment movement in the SlavíčRiver catchment.However,the modelling provided valuable information about high sediment connectivity despite different recent land use conditions(highly forested area of the catchment)than those in historical times from the 16th to 19th centuries when the SlavíčRiver catchment was highly deforested and sediment connectivity was probably higher.The analysis of anthropogenic interventions,field mapping,grain size of bed sediments and stream power analysis revealed more deceleration of sediment movement through the catchment,decreased sediment connectivity with bed erosion,and gradual river channel process transformation in some reaches.Field mapping has identified various natural formations and human-induced changes impacting the longitudinal and lateral connectivity in the SlavíčRiver.For instance,embankments along 48%of the river's length,both on the right and left banks,significantly hinder lateral sediment supply to the channel.Stream power index analysis indicates increased energy levels in the flowing water in the river's upper reaches(up to 404.8 W m^(-2)).This high energy is also observed in certain downstream sections(up to 337.6 W m^(-2)),where it is influenced by human activities.These conditions lead to intensified erosion processes,playing a crucial role in sediment connectivity.Similar observations were described in recent studies that pointed out the long-term human interventions on many streams draining European mountains,where a decrease in sediment connectivity in these streams is linked with sediment deficits and the transformation of processes forming channels.
