The Experts below are selected from a list of 279 Experts worldwide ranked by ideXlab platform
M. Higuchi - One of the best experts on this subject based on the ideXlab platform.
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Regulation of Mitochondrial DNA content and cancer.
Mitochondrion, 2006Co-Authors: M. HiguchiAbstract:Abstract Enzymatic activities of the proteins encoded in nuclear genome are regulated by transcriptional, translational and post-transcriptional level. Enzymatic activities of proteins encoded in Mitochondrial DNA (mtDNA) have been considered to be regulated by the same steps although detailed mechanisms might differ. However, dynamic change of the number of mtDNA, from some hundred to more than ten thousand, should be considered as another novel mechanism to regulate mtDNA-encoded proteins. Recently, we showed the connection of mtDNA depletion and deletion to cancer progression [Higuchi, M., Kudo, T., Suzuki, S., Evans, T.T., Sasaki, R., Wada, Y., Shirakawa, T., Sawyer, J.R., Gotoh, A., 2006. Mitochondrial DNA determines androgen dependence in prostate cancer cell lines. Oncogene 25, 1437–1445]. This review focuses and describes the possible connections of the Mitochondrial DNA depletion and deletion to cancer.
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Mitochondrial DNA determines androgen dependence in prostate cancer cell lines
Oncogene, 2006Co-Authors: M. Higuchi, T T Evans, J R Sawyer, T Shirakawa, T. Kudo, R Sasaki, S Suzuki, Y Wada, A GotohAbstract:Prostate cancer progresses from an androgen-dependent to androgen-independent stage after androgen ablation therapy. Mitochondrial DNA plays a role in cell death and metastatic competence. Further, heteroplasmic large-deletion Mitochondrial DNA is very common in prostate cancer. To investigate the role of Mitochondrial DNA in androgen dependence of prostate cancers, we tested the changes of normal and deleted Mitochondrial DNA in accordance with the progression of prostate cancer. We demonstrated that the androgen-independent cell line C4-2, established by inoculation of the androgen-dependent LNCaP cell line into castrated mice, has a greatly reduced amount of normal Mitochondrial DNA and an accumulation of large-deletion DNA. Strikingly, the depletion of Mitochondrial DNA from androgen-dependent LNCaP resulted in a loss of androgen dependence. Reconstitution of normal Mitochondrial DNA to the Mitochondrial DNA-depleted clone restored androgen dependence. These results indicate that Mitochondrial DNA determines androgen dependence of prostate cancer cell lines. Further, Mitochondrial DNA-deficient cells formed tumors in castrated athymic mice, whereas LNCaP did not. The accumulation of large deletion and depletion of Mitochondrial DNA may thus play a role in the development of androgen independence, leading to progression of prostate cancers.
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Mitochondrial DNA determines androgen sensitivity in prostate cancer cell lines
Cancer Research, 2005Co-Authors: M. Higuchi, T T Evans, T Shirakawa, T. Kudo, Y Wada, A GotohAbstract:1024 Prostate cancer progresses from an androgen-dependent stage to androgen-independent after androgen ablation therapy. Mitochondrial DNA plays a role in cell death and metastatic competence. Further, heteroplasmic large deletion Mitochondrial DNA is very common in prostate cancer. To investigate the role of Mitochondrial DNA in androgen dependence of prostate cancers, we tested the changes of normal and deleted Mitochondrial DNA in accordance with the progression of prostate cancer. We demonstrate that androgen-independent cell line C4-2, established by inoculation of androgen-dependent LNCaP into castrated mice, as compared with LNCaP, have 8 times reduced expression of normal Mitochondrial DNA associated with an accumulation of large deletion. C4-2 has a marked decrease in respiratory function possibly due to the change of Mitochondrial DNA. Strikingly, depletion of Mitochondrial DNA from androgen-dependent LNCaP resulted in a loss of androgen dependence. Reconstitution of normal Mitochondrial DNA to Mitochondrial DNA-depleted clone restored androgen dependence. These results indicate that Mitochondrial DNA determines androgen dependence of prostate cancer cell lines. Further, Mitochondrial DNA-deficient cells formed tumors in castrated athymic mice, whereas LNCaP did not. The accumulation of large deletion and depletion of Mitochondrial DNA may thus play a role in the development of androgen independence and progression of prostate cancers.
Michael P. Yaffe - One of the best experts on this subject based on the ideXlab platform.
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Mitochondrial DNA inheritance in Saccharomyces cerevisiae.
Trends in microbiology, 2000Co-Authors: Karen H. Berger, Michael P. YaffeAbstract:Respiratory metabolism depends on Mitochondrial DNA, yet the mechanisms that ensure the inheritance of the Mitochondrial genome are largely obscure. Recent studies with Saccharomyces cerevisiae suggest that distinct factors mediate the active segregation of Mitochondrial DNA during mitotic growth. The identification of the proteins required for the maintenance of the Mitochondrial genome provides clues to the mechanisms of, and molecular machinery involved in, Mitochondrial DNA inheritance.
A Gotoh - One of the best experts on this subject based on the ideXlab platform.
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Mitochondrial DNA determines androgen dependence in prostate cancer cell lines
Oncogene, 2006Co-Authors: M. Higuchi, T T Evans, J R Sawyer, T Shirakawa, T. Kudo, R Sasaki, S Suzuki, Y Wada, A GotohAbstract:Prostate cancer progresses from an androgen-dependent to androgen-independent stage after androgen ablation therapy. Mitochondrial DNA plays a role in cell death and metastatic competence. Further, heteroplasmic large-deletion Mitochondrial DNA is very common in prostate cancer. To investigate the role of Mitochondrial DNA in androgen dependence of prostate cancers, we tested the changes of normal and deleted Mitochondrial DNA in accordance with the progression of prostate cancer. We demonstrated that the androgen-independent cell line C4-2, established by inoculation of the androgen-dependent LNCaP cell line into castrated mice, has a greatly reduced amount of normal Mitochondrial DNA and an accumulation of large-deletion DNA. Strikingly, the depletion of Mitochondrial DNA from androgen-dependent LNCaP resulted in a loss of androgen dependence. Reconstitution of normal Mitochondrial DNA to the Mitochondrial DNA-depleted clone restored androgen dependence. These results indicate that Mitochondrial DNA determines androgen dependence of prostate cancer cell lines. Further, Mitochondrial DNA-deficient cells formed tumors in castrated athymic mice, whereas LNCaP did not. The accumulation of large deletion and depletion of Mitochondrial DNA may thus play a role in the development of androgen independence, leading to progression of prostate cancers.
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Mitochondrial DNA determines androgen sensitivity in prostate cancer cell lines
Cancer Research, 2005Co-Authors: M. Higuchi, T T Evans, T Shirakawa, T. Kudo, Y Wada, A GotohAbstract:1024 Prostate cancer progresses from an androgen-dependent stage to androgen-independent after androgen ablation therapy. Mitochondrial DNA plays a role in cell death and metastatic competence. Further, heteroplasmic large deletion Mitochondrial DNA is very common in prostate cancer. To investigate the role of Mitochondrial DNA in androgen dependence of prostate cancers, we tested the changes of normal and deleted Mitochondrial DNA in accordance with the progression of prostate cancer. We demonstrate that androgen-independent cell line C4-2, established by inoculation of androgen-dependent LNCaP into castrated mice, as compared with LNCaP, have 8 times reduced expression of normal Mitochondrial DNA associated with an accumulation of large deletion. C4-2 has a marked decrease in respiratory function possibly due to the change of Mitochondrial DNA. Strikingly, depletion of Mitochondrial DNA from androgen-dependent LNCaP resulted in a loss of androgen dependence. Reconstitution of normal Mitochondrial DNA to Mitochondrial DNA-depleted clone restored androgen dependence. These results indicate that Mitochondrial DNA determines androgen dependence of prostate cancer cell lines. Further, Mitochondrial DNA-deficient cells formed tumors in castrated athymic mice, whereas LNCaP did not. The accumulation of large deletion and depletion of Mitochondrial DNA may thus play a role in the development of androgen independence and progression of prostate cancers.
Laurie S. Kaguni - One of the best experts on this subject based on the ideXlab platform.
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Matrix proteases in Mitochondrial DNA function.
Biochimica et biophysica acta, 2011Co-Authors: Yuichi Matsushima, Laurie S. KaguniAbstract:Lon, ClpXP and m-AAA are the three major ATP-dependent proteases in the Mitochondrial matrix. All three are involved in general quality control by degrading damaged or abnormal proteins. In addition to this role, they are proposed to serve roles in Mitochondrial DNA functions including packaging and stability, replication, transcription and translation. In particular, Lon has been implicated in mtDNA metabolism in yeast, fly and humans. Here, we review the role of Lon protease in Mitochondrial DNA functions, and discuss a putative physiological role for Mitochondrial transcription factor A (TFAM) degradation by Lon protease. We also discuss the possible roles of m-AAA and ClpXP in Mitochondrial DNA functions, and the putative candidate substrates for the three matrix proteases. This article is part of a Special Issue entitled: Mitochondrial Gene Expression.
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Modular architecture of the hexameric human Mitochondrial DNA helicase.
Journal of molecular biology, 2007Co-Authors: Tawn D. Ziebarth, Carol L. Farr, Laurie S. KaguniAbstract:Abstract We have probed the structure of the human Mitochondrial DNA helicase, an enzyme that uses the energy of nucleotide hydrolysis to unwind duplex DNA during Mitochondrial DNA replication. This novel helicase shares substantial amino acid sequence and functional similarities with the bacteriophage T7 primase-helicase. We show in velocity sedimentation and gel filtration analyses that the Mitochondrial DNA helicase exists as a hexamer. Limited proteolysis by trypsin results in the production of several stable fragments, and N-terminal sequencing reveals distinct N and C-terminal polypeptides that represent minimal structural domains. Physical analysis of the proteolytic products defines the region required to maintain oligomeric structure to reside within amino acid residues ∼405–590. Truncations of the N and C termini affect differentially DNA-dependent ATPase activity, and whereas a C-terminal domain polypeptide is functional, an N-terminal domain polypeptide lacks ATPase activity. Sequence similarity and secondary structural alignments combined with biochemical data suggest that amino acid residue R609 serves as the putative arginine finger that is essential for ATPase activity in ring helicases. The hexameric conformation and modular architecture revealed in our study document that the Mitochondrial DNA helicase and bacteriophage T7 primase-helicase share physical features. Our findings place the Mitochondrial DNA helicase firmly in the DNAB-like family of replicative DNA helicases.
Karen H. Berger - One of the best experts on this subject based on the ideXlab platform.
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Mitochondrial DNA inheritance in Saccharomyces cerevisiae.
Trends in microbiology, 2000Co-Authors: Karen H. Berger, Michael P. YaffeAbstract:Respiratory metabolism depends on Mitochondrial DNA, yet the mechanisms that ensure the inheritance of the Mitochondrial genome are largely obscure. Recent studies with Saccharomyces cerevisiae suggest that distinct factors mediate the active segregation of Mitochondrial DNA during mitotic growth. The identification of the proteins required for the maintenance of the Mitochondrial genome provides clues to the mechanisms of, and molecular machinery involved in, Mitochondrial DNA inheritance.
