Prohibitin(PHB) participates in several biological processes including apoptosis, transcription regulation and suppression of cell proliferation in mammals. In this study, we cloned the full-length c DNA of prohibitin...Prohibitin(PHB) participates in several biological processes including apoptosis, transcription regulation and suppression of cell proliferation in mammals. In this study, we cloned the full-length c DNA of prohibitin 2(Cf-phb2) from the testis of scallop(Chlamys farreri). The deduced amino acid sequence presented a characteristic of PHB family with the PHB domain, and clustered with PHB2 of other species. Temporal and spatial expression of Cf-phb2 in testis during the reproductive cycle was detected by quantitative real-time PCR(q RT-PCR) and in situ hybridization. The expression of Cf-phb2 in the testis increased when testis developed from the resting stage to mature stage. The m RNA abundance of Cf-phb2 was the highest at mature stage, which was about 15-fold higher than that at proliferative stage. The expression of Cf-phb2 could be detected by in situ hybridization in all types of germ cells in testis, including spermatogonia, spermatocytes, spermatids and spermatozoa. The intensity of the signal increased with the spermatogenesis and was the highest in spermatids, which suggested that CF-PHB2 might affect the spermatogenesis of C. farreri.展开更多
Disruption of the mitochondrial quality surveillance(MQS)system contributes to mitochondrial dysfunction in diabetic cardiomyopathy(DCM).In this study,we observed that cardiac expression of phosphoglycerate mutase 5(P...Disruption of the mitochondrial quality surveillance(MQS)system contributes to mitochondrial dysfunction in diabetic cardiomyopathy(DCM).In this study,we observed that cardiac expression of phosphoglycerate mutase 5(PGAM5),a mitochondrial Ser/Thr protein phosphatase,is upregulated in mice with streptozotocin-induced DCM.Notably,DCM-related cardiac structural and functional deficits were negated in cardiomyocyte-specific Pgam5 knockout(Pgam5^(CKO))mice.Hyperglycemic stress impaired adenosine triphosphate production,reduced respiratory activity,and prolonged mitochondrial permeability transition pore opening in acutely isolated neonatal cardiomyocytes from control Pgam5^(f/f) mice,and these effects were markedly prevented in cardiomyocytes from Pgam5^(CKO) mice.Likewise,three main MQS-governed processes—namely,mitochondrial fission/fusion cycling,mitophagy,and biogenesis—were disrupted by hyperglycemia in Pgam5^(f/f),but not in Pgam5^(CKO),cardiomyocytes.On the basis of bioinformatics prediction of interaction between PGAM5 and prohibitin 2(PHB2),an inner mitochondrial membrane-associated scaffolding protein,co-immunoprecipitation,and immunoblot assays demonstrated that PGAM5 dephosphorylates PHB2 on Ser91.Transfection of cardiomyocytes with phosphodefective or phosphomimetic Ser91 mutants of PHB2 confirmed a critical role for PGAM5-mediated dephosphorylation of PHB2 in mitochondrial dysfunction associated with hyperglycemic stress.Furthermore,knockin mice expressing phosphomimetic PHB2^(S91D) were resistant to diabetes-induced cardiac dysfunction.Our findings highlight the PGAM-PHB2 axis as a novel and critical regulator of mitochondrial dysfunction in DCM.展开更多
基金supported by the National High Technology Research and Development Program of China(863 Program)(2012AA10A402)the Natural Science Foundation of Qingdao(11-2-4-1(10)-jch)
文摘Prohibitin(PHB) participates in several biological processes including apoptosis, transcription regulation and suppression of cell proliferation in mammals. In this study, we cloned the full-length c DNA of prohibitin 2(Cf-phb2) from the testis of scallop(Chlamys farreri). The deduced amino acid sequence presented a characteristic of PHB family with the PHB domain, and clustered with PHB2 of other species. Temporal and spatial expression of Cf-phb2 in testis during the reproductive cycle was detected by quantitative real-time PCR(q RT-PCR) and in situ hybridization. The expression of Cf-phb2 in the testis increased when testis developed from the resting stage to mature stage. The m RNA abundance of Cf-phb2 was the highest at mature stage, which was about 15-fold higher than that at proliferative stage. The expression of Cf-phb2 could be detected by in situ hybridization in all types of germ cells in testis, including spermatogonia, spermatocytes, spermatids and spermatozoa. The intensity of the signal increased with the spermatogenesis and was the highest in spermatids, which suggested that CF-PHB2 might affect the spermatogenesis of C. farreri.
基金the Natural Science Foundation of Guangdong Province,China(grant number 2016A030313792)the Basic and Applied Basic Research Project of Guangzhou University Joint Project(no.202201020605)the National Natural Science Foundation of China(82270279 and 82200296).
文摘Disruption of the mitochondrial quality surveillance(MQS)system contributes to mitochondrial dysfunction in diabetic cardiomyopathy(DCM).In this study,we observed that cardiac expression of phosphoglycerate mutase 5(PGAM5),a mitochondrial Ser/Thr protein phosphatase,is upregulated in mice with streptozotocin-induced DCM.Notably,DCM-related cardiac structural and functional deficits were negated in cardiomyocyte-specific Pgam5 knockout(Pgam5^(CKO))mice.Hyperglycemic stress impaired adenosine triphosphate production,reduced respiratory activity,and prolonged mitochondrial permeability transition pore opening in acutely isolated neonatal cardiomyocytes from control Pgam5^(f/f) mice,and these effects were markedly prevented in cardiomyocytes from Pgam5^(CKO) mice.Likewise,three main MQS-governed processes—namely,mitochondrial fission/fusion cycling,mitophagy,and biogenesis—were disrupted by hyperglycemia in Pgam5^(f/f),but not in Pgam5^(CKO),cardiomyocytes.On the basis of bioinformatics prediction of interaction between PGAM5 and prohibitin 2(PHB2),an inner mitochondrial membrane-associated scaffolding protein,co-immunoprecipitation,and immunoblot assays demonstrated that PGAM5 dephosphorylates PHB2 on Ser91.Transfection of cardiomyocytes with phosphodefective or phosphomimetic Ser91 mutants of PHB2 confirmed a critical role for PGAM5-mediated dephosphorylation of PHB2 in mitochondrial dysfunction associated with hyperglycemic stress.Furthermore,knockin mice expressing phosphomimetic PHB2^(S91D) were resistant to diabetes-induced cardiac dysfunction.Our findings highlight the PGAM-PHB2 axis as a novel and critical regulator of mitochondrial dysfunction in DCM.
