Mitochondria are crucial in sustaining and orchestrating cellular functions.Capitalizing on this,we explored mitochondrial transplantation as an innovative therapeutic strategy for acute spinal cord injury(SCI).In our...Mitochondria are crucial in sustaining and orchestrating cellular functions.Capitalizing on this,we explored mitochondrial transplantation as an innovative therapeutic strategy for acute spinal cord injury(SCI).In our study,we developed an engineered mitochondrial compound tailored to target macrophages within the SCI region.Sourced from IL-10-induced Mertkhi bone marrow-derived macrophages,we conjugated a peptide sequence,cations-cysteine-alanine-glutamine-lysine(CAQK),with the mitochondria,optimizing its targeting affinity for the injury site.Our data demonstrated that these compounds significantly enhanced macrophage phagocytosis of myelin debris,curtailed lipid buildup,ameliorated mitochondrial dysfunction,and attenuated pro-inflammatory profiles in macrophages,both in vitro and in vivo.The intravenously delivered mitochondrial compounds targeted the SCI epicenter,with macrophages being the primary recipients.Critically,they promoted tissue regeneration and bolstered functional recovery in SCI mice.This study heralds a transformative approach to mitochondrial transplantation in SCI,spotlighting the modulation of macrophage activity,phagocytosis,and phenotype.展开更多
The endoplasmic reticulum(ER)functions as a quality-control organelle for protein homeostasis,or"proteostasis".The protein quality control systems involve ER-associated degradation,protein chaperons,and auto...The endoplasmic reticulum(ER)functions as a quality-control organelle for protein homeostasis,or"proteostasis".The protein quality control systems involve ER-associated degradation,protein chaperons,and autophagy.展开更多
基金supported by the Key Program of the National Natural Science Foundation of China(No.82030071)the National Natural Science Foundation of China(No.82202722,No.81874004)+3 种基金the Science and Technology Major Project of Changsha(No.kh2103008)the Science Foundation of Xiangya Hospital for Young Scholar(Grant No.2021q18)the Natural Science Foundation of Changsha city(Grant No.kq2202378)Graduate students of Central South University independently explore innovative projects(2022ZZTS094).
文摘Mitochondria are crucial in sustaining and orchestrating cellular functions.Capitalizing on this,we explored mitochondrial transplantation as an innovative therapeutic strategy for acute spinal cord injury(SCI).In our study,we developed an engineered mitochondrial compound tailored to target macrophages within the SCI region.Sourced from IL-10-induced Mertkhi bone marrow-derived macrophages,we conjugated a peptide sequence,cations-cysteine-alanine-glutamine-lysine(CAQK),with the mitochondria,optimizing its targeting affinity for the injury site.Our data demonstrated that these compounds significantly enhanced macrophage phagocytosis of myelin debris,curtailed lipid buildup,ameliorated mitochondrial dysfunction,and attenuated pro-inflammatory profiles in macrophages,both in vitro and in vivo.The intravenously delivered mitochondrial compounds targeted the SCI epicenter,with macrophages being the primary recipients.Critically,they promoted tissue regeneration and bolstered functional recovery in SCI mice.This study heralds a transformative approach to mitochondrial transplantation in SCI,spotlighting the modulation of macrophage activity,phagocytosis,and phenotype.
基金This study was financially supported by The National Key Research and Development Program of China(grant number 2020YFC2008205)The National Natural Science Foundation of China(grant numbers 82171058,81974134,and 81974137)+1 种基金The Key R&D Plan of Hunan Province of China(No.2020SK2076)Natural Science Foundation of Hunan Province(No.2019JJ40507 and 2023JJ30956).
文摘The endoplasmic reticulum(ER)functions as a quality-control organelle for protein homeostasis,or"proteostasis".The protein quality control systems involve ER-associated degradation,protein chaperons,and autophagy.
