Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in th...Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria.Recent scholarly works,however,suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as intercellular or horizontal mitochondrial transfer.This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms.Specifically,we review the role of mitochondria transfer in regulating cellular metabolism restoration,excess reactive oxygen species(ROS)generation,proliferation,invasion,metastasis,mitophagy activation,mitochondrial DNA(mtDNA)inheritance,immune system modulation and therapeutic resistance in cancer.Additionally,we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.展开更多
BACKGROUND Recent studies have demonstrated that mesenchymal stem cells(MSCs)can rescue injured target cells via mitochondrial transfer.However,it has not been fully understood how bone marrow-derived MSCs repair glom...BACKGROUND Recent studies have demonstrated that mesenchymal stem cells(MSCs)can rescue injured target cells via mitochondrial transfer.However,it has not been fully understood how bone marrow-derived MSCs repair glomeruli in diabetic kidney disease(DKD).AIM To explore the mitochondrial transfer involved in the rescue of injured glomerular endothelial cells(GECs)by MSCs,both in vitro and in vivo.METHODS In vitro experiments were performed to investigate the effect of co-culture with MSCs on high glucose-induced GECs.The transfer of mitochondria was visualized using fluorescent microscopy.GECs were freshly sorted and ultimately tested for apoptosis,viability,mRNA expression by real-time reverse transcriptase-polymerase chain reaction,protein expression by western blot,and mitochondrial function.Moreover,streptozotocin-induced DKD rats were infused with MSCs,and renal function and oxidative stress were detected with an automatic biochemical analyzer and related-detection kits after 2 wk.Kidney histology was analyzed by hematoxylin and eosin,periodic acid-Schiff,and immunohistochemical staining.RESULTS Fluorescence imaging confirmed that MSCs transferred mitochondria to injured GECs when cocultured in vitro.We found that the apoptosis,proliferation,and mitochondrial function of injured GECs were improved following co-culture.Additionally,MSCs decreased pro-inflammatory cytokines[interleukin(IL)-6,IL-1β,and tumor necrosis factor-α]and pro-apoptotic factors(caspase 3 and Bax).Mitochondrial transfer also enhanced the expression of superoxide dismutase 2,B cell lymphoma-2,glutathione peroxidase(GPx)3,and mitofusin 2 and inhibited reactive oxygen species(ROS)and dynamin-related protein 1 expression.Furthermore,MSCs significantly ameliorated functional parameters(blood urea nitrogen and serum creatinine)and decreased the production of malondialdehyde,advanced glycation end products,and ROS,whereas they increased the levels of GPx and superoxide dismutase in vivo.In addition,significant reductions in the glomerular basement membrane and renal interstitial fibrosis were observed following MSC treatment.CONCLUSION MSCs can rejuvenate damaged GECs via mitochondrial transfer.Additionally,the improvement of renal function and pathological changes in DKD by MSCs may be related to the mechanism of mitochondrial transfer.展开更多
Recently, the definition of sepsis was concluded to be a life-threatening organ dysfunction caused by a dysregulated host response to infection. Severe patients always present with uncorrectable hypotension or hyperla...Recently, the definition of sepsis was concluded to be a life-threatening organ dysfunction caused by a dysregulated host response to infection. Severe patients always present with uncorrectable hypotension or hyperlactacidemia, which is defined as septic shock. The new definition emphasizes dysregulation of the host response and multiple organ dysfunction, which is partially attributed to metabolic disorders induced by energy crisis and oxidative stress. Mitochondria are a cellular organelle that are well known as the center of energy production, and mitochondrial damage or dysfunction is commonly induced in septic settings and is a predominant factor leading to a worse prognosis. In the present review, we determine the major mitochondrial disorders from morphology to functions in sepsis. In the following, several clinical or pre-clinical assays for monitoring mitochondrial function are demonstrated according to accumulated evidence, which is the first step of specific therapy targeting to modulate mitochondrial function. Accordingly, various reagents used for regulating mitochondrial enzyme activities and promoting biogenesis have been documented, among which mitochondriatargeted cation, TPP-conjugated antioxidants are the most valuable for future trials and clinical treatment to improve mitochondrial function as they may take advantage of the prognosis associated with septic complications.展开更多
Reconstructed embryos derived from intersubspecies somatic cell nuclear transfer （SCNT） have poorer developmental potential than those from intrasubspecies SCNT. Based on our previous study that Holstein dairy bovi...Reconstructed embryos derived from intersubspecies somatic cell nuclear transfer （SCNT） have poorer developmental potential than those from intrasubspecies SCNT. Based on our previous study that Holstein dairy bovine （HD） mitochondrial DNA （mtDNA） haplotype compatibility between donor karyoplast and recipient cytoplast is crucial for SCNT embryo development, we performed intersubspecies SCNT using HD as donor karyoplast and Luxi yellow heifer （LY） as recipient cytoplast according to mtDNA haplotypes determined by polymerase chain reaction- restriction fragment length polymorphism （PCR-RFLP） analysis. The results demonstrated that intersubspecies mtDNA homotype SCNT embryos had higher pre- and post-implantation developmental competence than intrasubspecies mtDNA heterotype embryos as well as improved blastocyst reprogramming status, including normal H3K9 dimethylation pattern and promoter hypomethylation of pluripotent genes such as Oct4 and Sox2, suggesting that intersubspecies SCNT using LY oocytes maintains HD cloning efficiency and may reprogram HD nuclei to develop into a normal cloned animal ultimately. Our results indicated that karyoplast-cytoplast interactions and mtDNA haplotype compatibility may affect bovine intersubspecies SCNT efficiency. This study on bovine intersubspecies SCNT is valuable for understanding the mechanisms of mtDNA haplotype compatibility between karyoplast and cytoplast impacting the bovine SCNT efficiency, and provides an alternative and economic resource for HD cloning.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.:82272749)the Natural Science Foundation of Liaoning Province,China(Grant No.:2022-MS-190).
文摘Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria.Recent scholarly works,however,suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as intercellular or horizontal mitochondrial transfer.This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms.Specifically,we review the role of mitochondria transfer in regulating cellular metabolism restoration,excess reactive oxygen species(ROS)generation,proliferation,invasion,metastasis,mitophagy activation,mitochondrial DNA(mtDNA)inheritance,immune system modulation and therapeutic resistance in cancer.Additionally,we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.
基金Supported by the Science and Technology Foundation of Jinhua,No.2021-4-190.
文摘BACKGROUND Recent studies have demonstrated that mesenchymal stem cells(MSCs)can rescue injured target cells via mitochondrial transfer.However,it has not been fully understood how bone marrow-derived MSCs repair glomeruli in diabetic kidney disease(DKD).AIM To explore the mitochondrial transfer involved in the rescue of injured glomerular endothelial cells(GECs)by MSCs,both in vitro and in vivo.METHODS In vitro experiments were performed to investigate the effect of co-culture with MSCs on high glucose-induced GECs.The transfer of mitochondria was visualized using fluorescent microscopy.GECs were freshly sorted and ultimately tested for apoptosis,viability,mRNA expression by real-time reverse transcriptase-polymerase chain reaction,protein expression by western blot,and mitochondrial function.Moreover,streptozotocin-induced DKD rats were infused with MSCs,and renal function and oxidative stress were detected with an automatic biochemical analyzer and related-detection kits after 2 wk.Kidney histology was analyzed by hematoxylin and eosin,periodic acid-Schiff,and immunohistochemical staining.RESULTS Fluorescence imaging confirmed that MSCs transferred mitochondria to injured GECs when cocultured in vitro.We found that the apoptosis,proliferation,and mitochondrial function of injured GECs were improved following co-culture.Additionally,MSCs decreased pro-inflammatory cytokines[interleukin(IL)-6,IL-1β,and tumor necrosis factor-α]and pro-apoptotic factors(caspase 3 and Bax).Mitochondrial transfer also enhanced the expression of superoxide dismutase 2,B cell lymphoma-2,glutathione peroxidase(GPx)3,and mitofusin 2 and inhibited reactive oxygen species(ROS)and dynamin-related protein 1 expression.Furthermore,MSCs significantly ameliorated functional parameters(blood urea nitrogen and serum creatinine)and decreased the production of malondialdehyde,advanced glycation end products,and ROS,whereas they increased the levels of GPx and superoxide dismutase in vivo.In addition,significant reductions in the glomerular basement membrane and renal interstitial fibrosis were observed following MSC treatment.CONCLUSION MSCs can rejuvenate damaged GECs via mitochondrial transfer.Additionally,the improvement of renal function and pathological changes in DKD by MSCs may be related to the mechanism of mitochondrial transfer.
基金supported by grants from the National Natural Science Foundation of China(No.81730057,81501698)the National Key Research and Development Program of China(No.2017YFC11003302)the Shenzhen San-ming Project(No.SZSM20162011)
文摘Recently, the definition of sepsis was concluded to be a life-threatening organ dysfunction caused by a dysregulated host response to infection. Severe patients always present with uncorrectable hypotension or hyperlactacidemia, which is defined as septic shock. The new definition emphasizes dysregulation of the host response and multiple organ dysfunction, which is partially attributed to metabolic disorders induced by energy crisis and oxidative stress. Mitochondria are a cellular organelle that are well known as the center of energy production, and mitochondrial damage or dysfunction is commonly induced in septic settings and is a predominant factor leading to a worse prognosis. In the present review, we determine the major mitochondrial disorders from morphology to functions in sepsis. In the following, several clinical or pre-clinical assays for monitoring mitochondrial function are demonstrated according to accumulated evidence, which is the first step of specific therapy targeting to modulate mitochondrial function. Accordingly, various reagents used for regulating mitochondrial enzyme activities and promoting biogenesis have been documented, among which mitochondriatargeted cation, TPP-conjugated antioxidants are the most valuable for future trials and clinical treatment to improve mitochondrial function as they may take advantage of the prognosis associated with septic complications.
基金This work was supported by the grants from the National High-Tech R&D Program of China(No.2007AA100502)the National Science and Technology Major Project of China (No.2008ZX08007-004)the National Natural Science Foundation of China(No.30770242)
文摘Reconstructed embryos derived from intersubspecies somatic cell nuclear transfer （SCNT） have poorer developmental potential than those from intrasubspecies SCNT. Based on our previous study that Holstein dairy bovine （HD） mitochondrial DNA （mtDNA） haplotype compatibility between donor karyoplast and recipient cytoplast is crucial for SCNT embryo development, we performed intersubspecies SCNT using HD as donor karyoplast and Luxi yellow heifer （LY） as recipient cytoplast according to mtDNA haplotypes determined by polymerase chain reaction- restriction fragment length polymorphism （PCR-RFLP） analysis. The results demonstrated that intersubspecies mtDNA homotype SCNT embryos had higher pre- and post-implantation developmental competence than intrasubspecies mtDNA heterotype embryos as well as improved blastocyst reprogramming status, including normal H3K9 dimethylation pattern and promoter hypomethylation of pluripotent genes such as Oct4 and Sox2, suggesting that intersubspecies SCNT using LY oocytes maintains HD cloning efficiency and may reprogram HD nuclei to develop into a normal cloned animal ultimately. Our results indicated that karyoplast-cytoplast interactions and mtDNA haplotype compatibility may affect bovine intersubspecies SCNT efficiency. This study on bovine intersubspecies SCNT is valuable for understanding the mechanisms of mtDNA haplotype compatibility between karyoplast and cytoplast impacting the bovine SCNT efficiency, and provides an alternative and economic resource for HD cloning.
