Recent studies have demonstrated that chloroplasts and mitochondria evoke specific Ca2＋ signals in response to biotic and abiotic stresses in a stress-dependent manner. The identification of Ca2＋ transporters and Ca...Recent studies have demonstrated that chloroplasts and mitochondria evoke specific Ca2＋ signals in response to biotic and abiotic stresses in a stress-dependent manner. The identification of Ca2＋ transporters and Ca2＋signaling mol- ecules in chloroplasts and mitochondria implies that they play roles in controlling not only intra-organellar functions, but also extra-organellar processes such as plant immunity and stress responses. It appears that organellar Ca2＋ signaling might be more important to plant cell functions than previously thought. This review briefly summarizes what is known about the molecular basis of Ca2＋ signaling in plant mitochondria and chloroplasts.展开更多
Mitochondria sense,shape and integrate signals,and thus function as central players in cellular signal transduction. Ca2+ waves and redox reactions are two such intracellular signals modulated by mitochondria. Mitocho...Mitochondria sense,shape and integrate signals,and thus function as central players in cellular signal transduction. Ca2+ waves and redox reactions are two such intracellular signals modulated by mitochondria. Mitochondrial Ca2+ transport is of utmost physio-pathological relevance with a strong impact on metabolism and cell fate. Despite its importance,the molecular nature of the proteins involvedin mitochondrial Ca2+ transport has been revealed only recently. Mitochondrial Ca2+ promotes energy metabolism through the activation of matrix dehydrogenases and downstream stimulation of the respiratory chain. These changes also alter the mitochondrial NAD(P)H/NAD(P)+ ratio,but at the same time will increase reactive oxygen species(ROS) production. Reducing equivalents and ROS are having opposite effects on the mitochondrial redox state,which are hard to dissect. With the recent development of genetically encoded mitochondrial-targeted redoxsensitive sensors,real-time monitoring of matrix thiol redox dynamics has become possible. The discoveries of the molecular nature of mitochondrial transporters of Ca2+ combined with the utilization of the novel redox sensors is shedding light on the complex relation between mitochondrial Ca2+ and redox signals and their impact on cell function. In this review,we describe mitochondrial Ca2+ handling,focusing on a number of newly identified proteins involved in mitochondrial Ca2+ uptake and release. We further discuss our recent findings,revealing how mitochondrial Ca2+ influences the matrix redox state. As a result,mitochondrial Ca2+ is able to modulate the many mitochondrial redox-regulated processes linked to normal physiology and disease.展开更多
Intracellular Ca2+ is vital for cell physiology.Disruption of Ca2+ homeostasis contributes to human diseases such as heart failure,neuron-degeneration,and diabetes.To ensure an effective intracellular Ca2+ dynamics,va...Intracellular Ca2+ is vital for cell physiology.Disruption of Ca2+ homeostasis contributes to human diseases such as heart failure,neuron-degeneration,and diabetes.To ensure an effective intracellular Ca2+ dynamics,various Ca2+ transport proteins localized in different cellular regions have to work in coordination.The central role of mitochondrial Ca2+ transport mechanisms in responding to physiological Ca2+ pulses in cytosol is to take up Ca2+ for regulating energy production and shaping the amplitude and duration of Ca2+ transients in various micro-domains.Since the discovery that isolated mitochondria can take up large quantities of Ca2+ approximately 5 decades ago,extensive studies have been focused on the functional characterization and implication of ion channels that dictate Ca2+ transport across the inner mitochondrial membrane.The mitochondrial Ca2+ uptake sensitive to non-specific inhibitors ruthenium red and Ru360 has long been considered as the activity of mitochondrial Ca2+ uniporter(MCU) .The general consensus is that MCU is dominantly or exclusively responsible for the mitochondrial Ca2+ influx.Since multiple Ca2+ influx mechanisms(e.g.L-,T-,and N-type Ca2+ channel) have their unique functions in the plasma membrane,it is plausible that mitochondrial inner membrane has more than just MCU to decode complex intracellular Ca2+ signaling in various cell types.During the last decade,four molecular identities related to mitochondrial Ca2+ influx mechanisms have been identified.These are mitochondrial ryanodine receptor,mitochondrial uncoupling proteins,LETM1(Ca2+ /H+ exchanger) ,and MCU and its Ca2+ sensing regulatory subunit MICU1.Here,we briefly review recent progress in these and other reported mitochondrial Ca2+ influx pathways and their differences in kinetics,Ca2+ dependence,and pharmacological characteristics.Their potential physiological and pathological implications are also discussed.展开更多
Cells are equipped with mechanisms to control tightly the influx, efflux and resting level of free calcium (Ca 2+ ). Inappropriate Ca 2+ signaling and abnormal Ca 2+ levels are involved in many clinical disorders incl...Cells are equipped with mechanisms to control tightly the influx, efflux and resting level of free calcium (Ca 2+ ). Inappropriate Ca 2+ signaling and abnormal Ca 2+ levels are involved in many clinical disorders including heart disease, Alzheimer's disease and stroke. Ca 2+ also plays a major role in cell growth, differentiation and motility; disturbances in these processes underlie cell transformation and the progression of cancer. Accordingly, research in the Strehler laboratory is focused on a better understanding of the molecular "toolkit" needed to ensure proper Ca 2+ homeostasis in the cell, as well as on the mechanisms of localized Ca 2+ signaling. A longterm focus has been on the plasma membrane calcium pumps (PMCAs), which are linked to multiple disorders including hearing loss, neurodegeneration, and heart disease. Our work over the past 20 years or more has revealed a surprising complexity of PMCA isoforms with different functional characteristics, regulation, and cellular localization. Emerging evidence shows how specific PMCAs contribute not only to setting basal intracellular Ca 2+ levels, but also to local Ca 2+ signaling and vectorial Ca 2+ transport. A second major research arearevolves around the calcium sensor protein calmodulin and an enigmatic calmodulin-like protein (CALML3) that is linked to epithelial differentiation. One of the cellular targets of CALML3 is the unconventional motor protein myosin-10, which raises new questions about the role of CALML3 and myosin-10 in cell adhesion and migration in normal cell differentiation and cancer.展开更多
This study was aimed to investigate the effects of dietary calcitriol or quercetin supplementation on eggshell and bone quality of laying hens.In trial 1,72 Hy-Line Brown layers(80-week-old)with weak-shelled strength(...This study was aimed to investigate the effects of dietary calcitriol or quercetin supplementation on eggshell and bone quality of laying hens.In trial 1,72 Hy-Line Brown layers(80-week-old)with weak-shelled strength(25 to 30 N)were assigned into 4 dietary treatments with 6 replicates of 3 birds and fed a basal diet(4%calcium level)or basal diets supplemented with 0.5%calcium,5μg/kg calcitriol or 500 mg/kg quercetin for 4 weeks.In trial 2,360 Hy-Line Brown layers(60-week-old)were divided into 3 groups with 8 replicates of 15 birds:control group(basal diet),calcitriol group(basal diet+5μg/kg calcitriol),and quercetin group(basal diet+500 mg/kg quercetin).This trial lasted for 12 weeks.The results showed that dietary calcitriol or quercetin improved eggshell quality in both trials(P<0.05).In trial 2,compared with the control group,both calcitriol and quercetin supplementations improved femoral bone quality,calcium retention of hens and calcium content in uterine fluid at 18.5 h post-oviposition(PO)(P<0.05),along with enhancing uterine morphology.Compared to the control group,supplemental calcitriol or quercetin up-regulated the relative mRNA expression levels of uterine transient receptor potential cation channel,subfamily V,member 6(TRPV6)at 8.5 h PO and plasma membrane calcium-ATPase(PMCA),vitamin D receptor(VDR),estrogen receptor alpha(ERα)at 18.5 h PO(P<0.05),but down-regulated the uterine caspase 3(CASP3)relative mRNA expression level at 8.5 h PO(P<0.05).Meanwhile,the femoral relative mRNA expression levels of tartrate-resistant acid phosphatase(TRAP)(up-regulated at 8.5 and 18.5 h PO)and alkaline phosphatase(ALP)(up-regulated at 8.5 h PO but down-regulated at 18.5 h PO)were also affected by calcitriol or quercetin supplementation(P<0.05).Compared to the calcitriol,quercetin increased hen-day egg production and femoral medullary bone volume/bone tissue volume but reduced femoral stiffness(P<0.05),which were accompanied by increased relative mRNA expression levels of uterine TRPV6,estrogen receptor beta(ERβ展开更多
Background Deteriorations in eggshell and bone quality are major challenges in aged laying hens.This study compared the differences of eggshell quality,bone parameters and their correlations as well as uterine physiol...Background Deteriorations in eggshell and bone quality are major challenges in aged laying hens.This study compared the differences of eggshell quality,bone parameters and their correlations as well as uterine physiologi-cal characteristics and the bone remodeling processes of hens laying eggs of different eggshell breaking strength to explore the mechanism of eggshell and bone quality reduction and their interaction.A total of 24074-week-old Hy-line Brown laying hens were selected and allocated to a high(HBS,44.83±1.31 N)or low(LBS,24.43±0.57 N)eggshell breaking strength group.Results A decreased thickness,weight and weight ratio of eggshells were observed in the LBS,accompanied with ultrastructural deterioration and total Ca reduction.Bone quality was negatively correlated with eggshell quality,marked with enhanced structures and increased components in the LBS.In the LBS,the mammillary knobs and effective layer grew slowly.At the initiation stage of eggshell calcification,a total of 130 differentially expressed genes(DEGs,122 upregulated and 8 downregulated)were identified in the uterus of hens in the LBS relative to those in the HBS.These DEGs were relevant to apoptosis due to the cellular Ca overload.Higher values of p62 protein level,caspase-8 activity,Bax protein expression and lower values of Bcl protein expression and Bcl/Bax ratio were seen in the LBS.TUNEL assay and hematoxylin-eosin staining showed a significant increase in TUNEL-positive cells and tissue damages in the uterus of the LBS.Although few DEGs were identified at the growth stage,similar uterine tissue damages were also observed in the LBS.The expressions of runt-related transcription factor 2 and osteocal-cin were upregulated in humeri of the LBS.Enlarged diameter and more structural damages of endocortical bones and decreased ash were observed in femurs of the HBS.Conclusion The lower eggshell breaking strength may be attributed to a declined Ca transport due to uterine tissue damages,which could affect eggshell calcification and lead t展开更多
文摘Recent studies have demonstrated that chloroplasts and mitochondria evoke specific Ca2＋ signals in response to biotic and abiotic stresses in a stress-dependent manner. The identification of Ca2＋ transporters and Ca2＋signaling mol- ecules in chloroplasts and mitochondria implies that they play roles in controlling not only intra-organellar functions, but also extra-organellar processes such as plant immunity and stress responses. It appears that organellar Ca2＋ signaling might be more important to plant cell functions than previously thought. This review briefly summarizes what is known about the molecular basis of Ca2＋ signaling in plant mitochondria and chloroplasts.
文摘Mitochondria sense,shape and integrate signals,and thus function as central players in cellular signal transduction. Ca2+ waves and redox reactions are two such intracellular signals modulated by mitochondria. Mitochondrial Ca2+ transport is of utmost physio-pathological relevance with a strong impact on metabolism and cell fate. Despite its importance,the molecular nature of the proteins involvedin mitochondrial Ca2+ transport has been revealed only recently. Mitochondrial Ca2+ promotes energy metabolism through the activation of matrix dehydrogenases and downstream stimulation of the respiratory chain. These changes also alter the mitochondrial NAD(P)H/NAD(P)+ ratio,but at the same time will increase reactive oxygen species(ROS) production. Reducing equivalents and ROS are having opposite effects on the mitochondrial redox state,which are hard to dissect. With the recent development of genetically encoded mitochondrial-targeted redoxsensitive sensors,real-time monitoring of matrix thiol redox dynamics has become possible. The discoveries of the molecular nature of mitochondrial transporters of Ca2+ combined with the utilization of the novel redox sensors is shedding light on the complex relation between mitochondrial Ca2+ and redox signals and their impact on cell function. In this review,we describe mitochondrial Ca2+ handling,focusing on a number of newly identified proteins involved in mitochondrial Ca2+ uptake and release. We further discuss our recent findings,revealing how mitochondrial Ca2+ influences the matrix redox state. As a result,mitochondrial Ca2+ is able to modulate the many mitochondrial redox-regulated processes linked to normal physiology and disease.
基金supported by NIH grants(Grant Nos.HL-033333 and HL093671)to Shey-Shing Sheu
文摘Intracellular Ca2+ is vital for cell physiology.Disruption of Ca2+ homeostasis contributes to human diseases such as heart failure,neuron-degeneration,and diabetes.To ensure an effective intracellular Ca2+ dynamics,various Ca2+ transport proteins localized in different cellular regions have to work in coordination.The central role of mitochondrial Ca2+ transport mechanisms in responding to physiological Ca2+ pulses in cytosol is to take up Ca2+ for regulating energy production and shaping the amplitude and duration of Ca2+ transients in various micro-domains.Since the discovery that isolated mitochondria can take up large quantities of Ca2+ approximately 5 decades ago,extensive studies have been focused on the functional characterization and implication of ion channels that dictate Ca2+ transport across the inner mitochondrial membrane.The mitochondrial Ca2+ uptake sensitive to non-specific inhibitors ruthenium red and Ru360 has long been considered as the activity of mitochondrial Ca2+ uniporter(MCU) .The general consensus is that MCU is dominantly or exclusively responsible for the mitochondrial Ca2+ influx.Since multiple Ca2+ influx mechanisms(e.g.L-,T-,and N-type Ca2+ channel) have their unique functions in the plasma membrane,it is plausible that mitochondrial inner membrane has more than just MCU to decode complex intracellular Ca2+ signaling in various cell types.During the last decade,four molecular identities related to mitochondrial Ca2+ influx mechanisms have been identified.These are mitochondrial ryanodine receptor,mitochondrial uncoupling proteins,LETM1(Ca2+ /H+ exchanger) ,and MCU and its Ca2+ sensing regulatory subunit MICU1.Here,we briefly review recent progress in these and other reported mitochondrial Ca2+ influx pathways and their differences in kinetics,Ca2+ dependence,and pharmacological characteristics.Their potential physiological and pathological implications are also discussed.
基金Supported by The National Institutes of Health (NS51769)the Mayo Foundation for Education and Research
文摘Cells are equipped with mechanisms to control tightly the influx, efflux and resting level of free calcium (Ca 2+ ). Inappropriate Ca 2+ signaling and abnormal Ca 2+ levels are involved in many clinical disorders including heart disease, Alzheimer's disease and stroke. Ca 2+ also plays a major role in cell growth, differentiation and motility; disturbances in these processes underlie cell transformation and the progression of cancer. Accordingly, research in the Strehler laboratory is focused on a better understanding of the molecular "toolkit" needed to ensure proper Ca 2+ homeostasis in the cell, as well as on the mechanisms of localized Ca 2+ signaling. A longterm focus has been on the plasma membrane calcium pumps (PMCAs), which are linked to multiple disorders including hearing loss, neurodegeneration, and heart disease. Our work over the past 20 years or more has revealed a surprising complexity of PMCA isoforms with different functional characteristics, regulation, and cellular localization. Emerging evidence shows how specific PMCAs contribute not only to setting basal intracellular Ca 2+ levels, but also to local Ca 2+ signaling and vectorial Ca 2+ transport. A second major research arearevolves around the calcium sensor protein calmodulin and an enigmatic calmodulin-like protein (CALML3) that is linked to epithelial differentiation. One of the cellular targets of CALML3 is the unconventional motor protein myosin-10, which raises new questions about the role of CALML3 and myosin-10 in cell adhesion and migration in normal cell differentiation and cancer.
基金supported by the National Natural Science Foundation of China (32172743)the eammarked fund for China Agriculture Research Systems (CARS-40)the Agricultural Science and Tec hnology Innovation Program (ASTIP)of CAAS.
文摘This study was aimed to investigate the effects of dietary calcitriol or quercetin supplementation on eggshell and bone quality of laying hens.In trial 1,72 Hy-Line Brown layers(80-week-old)with weak-shelled strength(25 to 30 N)were assigned into 4 dietary treatments with 6 replicates of 3 birds and fed a basal diet(4%calcium level)or basal diets supplemented with 0.5%calcium,5μg/kg calcitriol or 500 mg/kg quercetin for 4 weeks.In trial 2,360 Hy-Line Brown layers(60-week-old)were divided into 3 groups with 8 replicates of 15 birds:control group(basal diet),calcitriol group(basal diet+5μg/kg calcitriol),and quercetin group(basal diet+500 mg/kg quercetin).This trial lasted for 12 weeks.The results showed that dietary calcitriol or quercetin improved eggshell quality in both trials(P<0.05).In trial 2,compared with the control group,both calcitriol and quercetin supplementations improved femoral bone quality,calcium retention of hens and calcium content in uterine fluid at 18.5 h post-oviposition(PO)(P<0.05),along with enhancing uterine morphology.Compared to the control group,supplemental calcitriol or quercetin up-regulated the relative mRNA expression levels of uterine transient receptor potential cation channel,subfamily V,member 6(TRPV6)at 8.5 h PO and plasma membrane calcium-ATPase(PMCA),vitamin D receptor(VDR),estrogen receptor alpha(ERα)at 18.5 h PO(P<0.05),but down-regulated the uterine caspase 3(CASP3)relative mRNA expression level at 8.5 h PO(P<0.05).Meanwhile,the femoral relative mRNA expression levels of tartrate-resistant acid phosphatase(TRAP)(up-regulated at 8.5 and 18.5 h PO)and alkaline phosphatase(ALP)(up-regulated at 8.5 h PO but down-regulated at 18.5 h PO)were also affected by calcitriol or quercetin supplementation(P<0.05).Compared to the calcitriol,quercetin increased hen-day egg production and femoral medullary bone volume/bone tissue volume but reduced femoral stiffness(P<0.05),which were accompanied by increased relative mRNA expression levels of uterine TRPV6,estrogen receptor beta(ERβ
基金This study was supported by the National Natural Science Foundation of China(32172743)China Agriculture Research System(CARS-40)the Agricultural Science and Technology Innovation Program(ASTIP)of CAAS.
文摘Background Deteriorations in eggshell and bone quality are major challenges in aged laying hens.This study compared the differences of eggshell quality,bone parameters and their correlations as well as uterine physiologi-cal characteristics and the bone remodeling processes of hens laying eggs of different eggshell breaking strength to explore the mechanism of eggshell and bone quality reduction and their interaction.A total of 24074-week-old Hy-line Brown laying hens were selected and allocated to a high(HBS,44.83±1.31 N)or low(LBS,24.43±0.57 N)eggshell breaking strength group.Results A decreased thickness,weight and weight ratio of eggshells were observed in the LBS,accompanied with ultrastructural deterioration and total Ca reduction.Bone quality was negatively correlated with eggshell quality,marked with enhanced structures and increased components in the LBS.In the LBS,the mammillary knobs and effective layer grew slowly.At the initiation stage of eggshell calcification,a total of 130 differentially expressed genes(DEGs,122 upregulated and 8 downregulated)were identified in the uterus of hens in the LBS relative to those in the HBS.These DEGs were relevant to apoptosis due to the cellular Ca overload.Higher values of p62 protein level,caspase-8 activity,Bax protein expression and lower values of Bcl protein expression and Bcl/Bax ratio were seen in the LBS.TUNEL assay and hematoxylin-eosin staining showed a significant increase in TUNEL-positive cells and tissue damages in the uterus of the LBS.Although few DEGs were identified at the growth stage,similar uterine tissue damages were also observed in the LBS.The expressions of runt-related transcription factor 2 and osteocal-cin were upregulated in humeri of the LBS.Enlarged diameter and more structural damages of endocortical bones and decreased ash were observed in femurs of the HBS.Conclusion The lower eggshell breaking strength may be attributed to a declined Ca transport due to uterine tissue damages,which could affect eggshell calcification and lead t
