Cardiomyocyte Specific Deletion of Crif1 Causes Mitochondrial Cardiomyopathy in Mice

Shin, Juhee; Lee, Seok Hong; Kwon, Min-Chul; Yang, Dong Kwon; Seo, Hwi Won; Kim, Jaetaek; Kim, Yoon Young; Im, Sun Kyoung; Kim, Kyong‐Tai; Park, Woo Jin; Kong, Young Yun

doi:10.1371/journal.pone.0053577

Cited by 14 publications

(19 citation statements)

References 41 publications

(78 reference statements)

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“…Therefore, homozygotic and heterozygotic loss of Crif1 in specific organs results in markedly or marginally reduced OxPhos capacities, respectively [18,36]. For example, homozygotic and heterozygotic Crif1-deficiency in adipose tissue produces widely variable disease phenotypes in vivo [18].…”

Section: Discussionmentioning

confidence: 99%

Disruption of CR6-interacting factor-1 (CRIF1) in mouse islet beta cells leads to mitochondrial diabetes with progressive beta cell failure

et al. 2015

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Aim/hypothesis Although mitochondrial oxidative phosphorylation (OxPhos) dysfunction is believed to be responsible for beta cell dysfunction in insulin resistance and mitochondrial diabetes, the mechanisms underlying progressive beta cell failure caused by defective mitochondrial OxPhos are largely unknown. Methods We examined the in vivo phenotypes of beta cell dysfunction in beta cell-specific Crif1 (also known as Gadd45gip1)-deficient mice. CR6-interacting factor-1 (CRIF1) is a mitochondrial protein essential for the synthesis and formation of the OxPhos complex in the inner mitochondrial membrane. Results Crif1beta−/− mice exhibited impaired glucose tolerance with defective insulin secretion as early as 4 weeks of age without defects in islet structure. At 11 weeks of age, Crif1 beta−/− mice displayed characteristic ultrastructural mitochondrial abnormalities as well as severe glucose intolerance. Furthermore, islet area and insulin content was decreased by approximately 50% compared with wild-type mice. Treatment with the glucoregulatory drug exenatide, a glucagon-like peptide-1 (GLP-1) agonist, was not sufficient to preserve beta cell function in Crif1 beta−/− mice. Conclusions/interpretation Our results indicate that mitochondrial OxPhos dysfunction triggers progressive beta cell failure that is not halted by treatment with a GLP-1 agonist. The Crif1 beta−/− mouse is a useful model for the study of beta cell failure caused by mitochondrial OxPhos dysfunction.

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Section: Discussionmentioning

confidence: 99%

Disruption of CR6-interacting factor-1 (CRIF1) in mouse islet beta cells leads to mitochondrial diabetes with progressive beta cell failure

et al. 2015

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“…Disruption of Crif1 in mouse islet beta cells leads to mitochondrial diabetes with progressive beta cell failure [31]. Finally, cardiomyocyte specific deletion of Crif1 causes mitochondrial cardiomyopathy in mice [32]. Collectively, these reports of Crif1 ’s effect on mitochondrial function suggest that its impact on susceptibility to S .…”

Section: Discussionmentioning

confidence: 99%

“…This possibility is supported by the robust number of differentially expressed genes in the QTL region, by the allele-specific expression analysis, and by our discovery of several potential candidate genes. Second, the essential function maintaining mitochondrial homeostasis of host cell and oxidative phosphorylation [26, 30, 32] provides the possibility that Crif1 is merely a general host responsive factor coping with stress during inflammation. Third, S .…”

Section: Discussionmentioning

confidence: 99%

Candidate genes on murine chromosome 8 are associated with susceptibility to Staphylococcus aureus infection in mice and are involved with Staphylococcus aureus septicemia in humans

et al. 2017

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We previously showed that chromosome 8 of A/J mice was associated with susceptibility to S. aureus infection. However, the specific genes responsible for this susceptibility are unknown. Chromosome substitution strain 8 (CSS8) mice, which have chromosome 8 from A/J but an otherwise C57BL/6J genome, were used to identify the genetic determinants of susceptibility to S. aureus on chromosome 8. Quantitative trait loci (QTL) mapping of S. aureus-infected N2 backcross mice (F1 [C8A] × C57BL/6J) identified a locus 83180780–88103009 (GRCm38/mm10) on A/J chromosome 8 that was linked to S. aureus susceptibility. All genes on the QTL (n~ 102) were further analyzed by three different strategies: 1) different expression in susceptible (A/J) and resistant (C57BL/6J) mice only in response to S. aureus, 2) consistently different expression in both uninfected and infected states between the two strains, and 3) damaging non-synonymous SNPs in either strain. Eleven candidate genes from the QTL region were significantly differently expressed in patients with S. aureus infection vs healthy human subjects. Four of these 11 genes also exhibited significantly different expression in S. aureus-challenged human neutrophils: Ier2, Crif1, Cd97 and Lyl1. CD97 ligand binding was evaluated within peritoneal neutrophils from A/J and C57BL/6J. CD97 from A/J had stronger CD55 but weaker integrin α5β1 ligand binding as compared with C57BL/6J. Because CD55/CD97 binding regulates immune cell activation and cytokine production, and integrin α5β1 is a membrane receptor for fibronectin, which is also bound by S. aureus, strain-specific differences could contribute to susceptibility to S. aureus. Down-regulation of Crif1 with siRNA was associated with increased host cell apoptosis among both naïve and S. aureus-infected bone marrow-derived macrophages. Specific genes in A/J chromosome 8, including Cd97 and Crif1, may play important roles in host defense against S. aureus.

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“…Recent studies suggest that CRIF1 has a role in oxidative phosphorylation through the integration of polypeptides into the mitochondrial membrane (Kim et al, 2012l; Shin et al 2013) and that is part of the mammalian ribosome (Koc et al 2013). In addition, CRIF1 has a role in oxidative phosphorylation in mouse adipose tissue (Ryu et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of androgen receptor corepression by CKβBP2/CRIF1, a multifunctional transcription factor coregulator expressed in prostate cancer

Tan¹,

Bai²,

Grossman³

et al. 2014

Molecular and Cellular Endocrinology

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The transcription factor coregulator Casein kinase IIβbinding protein 2 or CR6-interacting factor 1 (CKβBP2/CRIF1) binds the androgen receptor (AR) in prostate cancer cells and in response to dihydrotestosterone localizes with AR on the prostate-specific antigen gene enhancer, but does not bind DNA suggesting CKβBP2/CRIF1 localization in chromatin is determined by AR. In this study we show also that CKβBP2/CRIF1 inhibits wild-type AR and AR N-terminal transcriptional activity, binds to the AR C-terminal region, inhibits interaction of the AR N- and C-terminal domains (N/C interaction) and competes with p160 coactivator binding to the AR C-terminal domain, suggesting CKβBP2/CRIF1 interferes with AR activation functions 1 and 2. CKβBP2/CRIF1 is expressed mainly in stromal cells of benign prostatic hyperplasia and in stroma and epithelium of prostate cancer. CKβBP2/CRIF1 protein is increased in epithelium of androgen-dependent prostate cancer compared to benign prostatic hyperplasia and decreased slightly in castration recurrent epithelium compared to androgen-dependent prostate cancer. The multifunctional CKβBP2/CRIF1 is a STAT3 interacting protein and reported to be a coactivator of STAT3. CKβBP2/CRIF1 is expressed with STAT3 in prostate cancer where STAT3 may help to offset the AR repressor effect of CKβBP2/CRIF1 and allow AR regulation of prostate cancer growth.

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Cardiomyocyte Specific Deletion of Crif1 Causes Mitochondrial Cardiomyopathy in Mice

Cited by 14 publications

References 41 publications

Disruption of CR6-interacting factor-1 (CRIF1) in mouse islet beta cells leads to mitochondrial diabetes with progressive beta cell failure

Disruption of CR6-interacting factor-1 (CRIF1) in mouse islet beta cells leads to mitochondrial diabetes with progressive beta cell failure

Candidate genes on murine chromosome 8 are associated with susceptibility to Staphylococcus aureus infection in mice and are involved with Staphylococcus aureus septicemia in humans

Mechanism of androgen receptor corepression by CKβBP2/CRIF1, a multifunctional transcription factor coregulator expressed in prostate cancer

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