Proteomics analysis of mitochondrial proteins reveals overexpression of a mitochondrial protein chaperon, prohibitin, in cells expressing hepatitis C virus core protein

Tsutsumi, Takeshi; Matsuda, Mami; Aizaki, Hideki; Moriya, Kyoji; Miyoshi, Hideyuki; Fujie, Hajime; Shintani, Yoshizumi; Yotsuyanagi, Hiroshi; Miyamura, Tatsuo; Suzuki, Tetsuro; Koike, Kazuhiko

doi:10.1002/hep.22998

Cited by 82 publications

(69 citation statements)

References 36 publications

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“…Our recent data suggest that epithelial PHB sustains anti-oxidant expression [44] and has anti-inflammatory properties such as reducing TNFa-stimulated NF-kB activation [42]. This is in agreement with emerging data that suggest a role of PHB in combating oxidative stress in multiple cells types [39,40,45,46]. In this study, we investigated the potential role of PHB in modulating mitochondrial stress-related autophagy in intestinal epithelial cells.…”

Section: Introductionsupporting

confidence: 83%

“…Given that the predominant subcellular localization of PHB is in the mitochondria in most cell types studied to date, emerging data suggest that PHB plays a role in stabilizing components of the electron transport chain [38]. Depletion of PHB function has been shown to cause electron transport chain disruption and increased intracellular oxidative stress [39,40]. As an indicator of intracellular ROS, Caco2-BBE cells transfected with siPHB or siNeg ctl were loaded with the oxidation-sensitive dye H 2 DCF-DA and assayed for DCF fluorescence 10, 20 and 30 minutes after loading using a plate reader.…”

Section: Phb Knockdown Increases Intracellular Reactive Oxygen Speciementioning

confidence: 99%

“…PHB is predominantly localized to the mitochondria in intestinal epithelial cells [37] and multiple studies have shown that PHB plays a role in maintaining normal mitochondrial function and morphology (reviewed in [38]). It has been shown that PHB interacts with complex I and subunits of cytochrome c oxidase of the respiratory chain and regulates their assembly [39,40]. Loss of PHB in mitochondria impairs function of the mitochondrial respiratory chain [39,40].…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that PHB interacts with complex I and subunits of cytochrome c oxidase of the respiratory chain and regulates their assembly [39,40]. Loss of PHB in mitochondria impairs function of the mitochondrial respiratory chain [39,40]. One obvious effect of respiratory chain dysfunction is increased oxidant production leading to oxidative stress, which can cause alterations in mitochondrial morphology and membrane potential [29].…”

Section: Introductionmentioning

confidence: 99%

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320 Prohibitin 1 Modulates Mitochondrial Stress-Related Autophagy in Human Colonic Epithelial Cells

Kathiria¹,

Butcher²,

Feagins³

et al. 2012

Gastroenterology

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Section: Introductionsupporting

confidence: 83%

Section: Phb Knockdown Increases Intracellular Reactive Oxygen Speciementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

320 Prohibitin 1 Modulates Mitochondrial Stress-Related Autophagy in Human Colonic Epithelial Cells

Kathiria¹,

Butcher²,

Feagins³

et al. 2012

Gastroenterology

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“…For HCC, various cancer genes, including tumor suppressor genes, oncogenes, and hepatitis B virus or hepatitis C virus (HCV) viral genes, have been employed for the development of mouse models. [134][135][136][137][138][139][140][141][142][143][144] More recently, miRNA-based mouse models predisposed to HCC have been reported. A transgenic mouse model characterized by overexpression of miR-221 in the liver was developed.…”

Section: Animal Models Of Liver Cancermentioning

confidence: 99%

MicroRNAs in liver cancer: a model for investigating pathogenesis and novel therapeutic approaches

et al. 2014

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MicroRNAs (miRNAs) constitute a large class of short RNAs (e.g., 20-24 nucleotides in length), whose main function is to posttranscriptionally regulate the expression of protein-coding genes. Their importance in tumorigenesis has been demonstrated over the past decade, and correspondingly, they have emerged as potential therapeutic molecules and targets. Liver cancer is one of the most common neoplastic diseases worldwide, and it currently has a poor prognosis owing to largely ineffective therapeutic options. Liver cancer is also an excellent model for testing miRNA-based therapy approaches as it can be easily targeted with the systemic delivery of oligonucleotides. In recent years, the role of miRNAs in hepatocellular carcinoma (HCC) has been established with molecular studies and the development of animal models. These studies have also provided the basis for evaluating the therapeutic potential of miRNAs, or anti-miRNAs. In general, the safety of miRNAs has been proven and antitumor activity has been observed. Moreover, because of the absence or presence of mild side effects, the prophylactic use of miRNA-based approaches may be foreseen.

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Liver-specific deletion of prohibitin 1 results in spontaneous liver injury, fibrosis, and hepatocellular carcinoma in mice

et al. 2010

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Prohibitin 1 (PHB1) is a highly conserved, ubiquitously expressed protein that participates in diverse processes including mitochondrial chaperone, growth and apoptosis. The role of PHB1 in vivo is unclear and whether it is a tumor suppressor is controversial. Mice lacking methionine adenosyltransferase 1A (MAT1A) have reduced PHB1 expression, impaired mitochondrial function, and spontaneously develop hepatocellular carcinoma (HCC). To see if reduced PHB1 expression contributes to the Mat1a knockout (KO) phenotype, we generated liver-specific Phb1 KO mice. Expression was determined at the messenger RNA and protein levels. PHB1 expression in cells was varied by small interfering RNA or overexpression. At 3 weeks, KO mice exhibit biochemical and histologic liver injury. Immunohistochemistry revealed apoptosis, proliferation, oxidative stress, fibrosis, bile duct epithelial metaplasia, hepatocyte dysplasia, and increased staining for stem cell and preneoplastic markers. Mitochondria are swollen and many have no discernible cristae. Differential gene expression revealed that genes associated with proliferation, malignant transformation, and liver fibrosis are highly up-regulated. From 20 weeks on, KO mice have multiple liver nodules and from 35 to 46 weeks, 38% have multifocal HCC. PHB1 protein levels were higher in normal human hepatocytes compared to human HCC cell lines Huh-7 and HepG2. Knockdown of PHB1 in murine nontransformed AML12 cells (normal mouse hepatocyte cell line) raised cyclin D1 expression, increased E2F transcription factor binding to cyclin D1 promoter, and proliferation. The opposite occurred with PHB1 overexpression. Knockdown or overexpression of PHB1 in Huh-7 cells did not affect proliferation significantly or sensitize cells to sorafenib-induced apoptosis. Conclusion: Hepatocyte-specific PHB1 deficiency results in marked liver injury, oxidative stress, and fibrosis with development of HCC by 8 months. These results support PHB1 as a tumor suppressor in hepatocytes. (HEPATOLOGY 2010;52:2096-2108 P rohibitin (PHB) proteins are highly conserved and ubiquitously expressed proteins that have diverse cellular functions.1,2 Two PHB proteins, PHB1 and PHB2, encoded by genes located on different chromosomes, form a large multimeric complex (PHB complex) that is found largely in the inner mitochondrial membrane where it exerts a chaperone-like function to stabilize newly synthesized mitochondrial

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Proteomics analysis of mitochondrial proteins reveals overexpression of a mitochondrial protein chaperon, prohibitin, in cells expressing hepatitis C virus core protein

Cited by 82 publications

References 36 publications

320 Prohibitin 1 Modulates Mitochondrial Stress-Related Autophagy in Human Colonic Epithelial Cells

320 Prohibitin 1 Modulates Mitochondrial Stress-Related Autophagy in Human Colonic Epithelial Cells

MicroRNAs in liver cancer: a model for investigating pathogenesis and novel therapeutic approaches

Liver-specific deletion of prohibitin 1 results in spontaneous liver injury, fibrosis, and hepatocellular carcinoma in mice

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