The homeostasis of vascular microenvironment is essential to maintain the normal vascular structure and function,while its disorder leads to vascular dysfunction,and cardiovascular and cerebrovascular diseases.Centros...The homeostasis of vascular microenvironment is essential to maintain the normal vascular structure and function,while its disorder leads to vascular dysfunction,and cardiovascular and cerebrovascular diseases.Centrosome is an important organelle existing in mammalian cells as well as the microtubule organizing center,playing an important role in maintaining vascular structure and homeostasis.This study reviewed the role of centrosome in the regulation of vascular microenvironmental homeostasis.Centrosomal proteins intricately regulate microtubule dynamics and stabilization,and diverse microtubule-relatived cellular activities,including the division,polarization and directional migration of vascular endothelial cells,smooth muscle cells and other types of cells.In addition,primary cilia formed by centrosome are essential in vascular microenvironment.Tumor endothelial cells usually acquire excess centrosomes,and excess centrosomes are regulated by several angiogenic factors.Therefore,uncovering the detailed molecular mechanisms underlying centrosome affecting vascular microenvironmental homeostasis are needed for the treatment of cardiovascular and cerebrovascular diseases.展开更多
An accurate map of intracellular organelle pH is crucial for comprehending cellular metabolism and organellar functions. However, a unified intracellular pH spectrum using a single probe is still lacking. Here, we dev...An accurate map of intracellular organelle pH is crucial for comprehending cellular metabolism and organellar functions. However, a unified intracellular pH spectrum using a single probe is still lacking. Here, we developed a novel quantum entanglement-enhanced pHsensitive probe called SITE-pHorin(single excitation and two emissions pH sensor protein), which features a wide pH-sensitive range and ratiometric quantitative measurement capabilities. We subsequently measured the pH of various organelles and their subcompartments, including mitochondrial subspaces, Golgi stacks, endoplasmic reticulum(ER), lysosomes, peroxisomes, and endosomes in COS-7 cells. For the long-standing debate on the pH of the mitochondrial compartments, we measured the pH of the mitochondrial cristae(mito-cristae) as 6.60±0.40, the pH of the mitochondrial intermembrane space(mito-IMS) as 6.95±0.30, and the pH of the two populations of the mitochondrial matrix(mito-matrix) at approximately 7.20±0.27 and 7.50±0.16, respectively. Notably, the pH of the lysosome exhibited a single, narrow Gaussian distribution centered at 4.79±0.17, which is consistent with an optimal lysosomal acidic pH between 4.5 and 5.0. Furthermore, quantum chemistry computations revealed that both the deprotonation of the residue Y182 and the discrete curvature of the deformed benzene ring in the chromophore are necessary for the quantum entanglement mechanism of SITE-pHorin. Intriguingly, our findings reveal an accurate pH gradient(0.6–0.9 pH units) between the mitochondrial cristae and the mitochondrial matrix, suggesting that prior knowledge about ∆p H(0.4–0.6) and the mitochondrial proton motive force(pmf) is underestimated.展开更多
文摘The homeostasis of vascular microenvironment is essential to maintain the normal vascular structure and function,while its disorder leads to vascular dysfunction,and cardiovascular and cerebrovascular diseases.Centrosome is an important organelle existing in mammalian cells as well as the microtubule organizing center,playing an important role in maintaining vascular structure and homeostasis.This study reviewed the role of centrosome in the regulation of vascular microenvironmental homeostasis.Centrosomal proteins intricately regulate microtubule dynamics and stabilization,and diverse microtubule-relatived cellular activities,including the division,polarization and directional migration of vascular endothelial cells,smooth muscle cells and other types of cells.In addition,primary cilia formed by centrosome are essential in vascular microenvironment.Tumor endothelial cells usually acquire excess centrosomes,and excess centrosomes are regulated by several angiogenic factors.Therefore,uncovering the detailed molecular mechanisms underlying centrosome affecting vascular microenvironmental homeostasis are needed for the treatment of cardiovascular and cerebrovascular diseases.
基金supported by the National Natural Science Foundation of China(92054103,32071137,32000855,32000522)the Funding for Scientific Research and Innovation Team of The First Affiliated Hospital of Zhengzhou University(ZYCXTD2023014)+1 种基金the Joint Construction Program for Medical Science and Technology Development of Henan Province of China(LHGJ20190239,2018020088)the Natural Science Foundation of Henan Province of China(202300410420)。
文摘An accurate map of intracellular organelle pH is crucial for comprehending cellular metabolism and organellar functions. However, a unified intracellular pH spectrum using a single probe is still lacking. Here, we developed a novel quantum entanglement-enhanced pHsensitive probe called SITE-pHorin(single excitation and two emissions pH sensor protein), which features a wide pH-sensitive range and ratiometric quantitative measurement capabilities. We subsequently measured the pH of various organelles and their subcompartments, including mitochondrial subspaces, Golgi stacks, endoplasmic reticulum(ER), lysosomes, peroxisomes, and endosomes in COS-7 cells. For the long-standing debate on the pH of the mitochondrial compartments, we measured the pH of the mitochondrial cristae(mito-cristae) as 6.60±0.40, the pH of the mitochondrial intermembrane space(mito-IMS) as 6.95±0.30, and the pH of the two populations of the mitochondrial matrix(mito-matrix) at approximately 7.20±0.27 and 7.50±0.16, respectively. Notably, the pH of the lysosome exhibited a single, narrow Gaussian distribution centered at 4.79±0.17, which is consistent with an optimal lysosomal acidic pH between 4.5 and 5.0. Furthermore, quantum chemistry computations revealed that both the deprotonation of the residue Y182 and the discrete curvature of the deformed benzene ring in the chromophore are necessary for the quantum entanglement mechanism of SITE-pHorin. Intriguingly, our findings reveal an accurate pH gradient(0.6–0.9 pH units) between the mitochondrial cristae and the mitochondrial matrix, suggesting that prior knowledge about ∆p H(0.4–0.6) and the mitochondrial proton motive force(pmf) is underestimated.
