Caspase cleavage of cytochrome c1 disrupts mitochondrial function and enhances cytochrome c release

Zhu, Yushan; Li, Min; Wang, Xiaohui; Jin, Haijing; Liu, Shusen; Xu, Jian‐Xin; Chen, Quan

doi:10.1038/cr.2011.82

Cited by 44 publications

(38 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The organization of the mitochondrial electron transport chain is a subject of intense debate at present, where two different models are being considered: the fluid model, that proposes a random organization for individual respiratory protein components, and the solid model, suggesting a stable association between individual complexes [6][7][8]. Apart their role in respiration, Cc and Cc 1 are clearly involved in the development of programmed cell death [9][10][11][12][13][14][15]. Such a dual role of Cc is regulated by post-translational modifications -namely, phosphorylation and nitration of tyrosine residues -that affect the binding of Cc to its physiological counterparts, either in the mitochondria or in the cytoplasm [16][17][18][19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Respiratory complexes III and IV can each bind two molecules of cytochrome c at low ionic strength

et al. 2015

View full text Add to dashboard Cite

a b s t r a c tThe transient interactions of respiratory cytochrome c with complexes III and IV is herein investigated by using heterologous proteins, namely human cytochrome c, the soluble domain of plant cytochrome c 1 and bovine cytochrome c oxidase. The binding molecular mechanisms of the resulting cross-complexes have been analyzed by Nuclear Magnetic Resonance and Isothermal Titration Calorimetry. Our data reveal that the two cytochrome c-involving adducts possess a 2:1 stoichiometry -that is, two cytochrome c molecules per adduct -at low ionic strength. We conclude that such extra binding sites at the surfaces of complexes III and IV can facilitate the turnover and sliding of cytochrome c molecules and, therefore, the electron transfer within respiratory supercomplexes.

show abstract

Section: Introductionmentioning

confidence: 99%

Respiratory complexes III and IV can each bind two molecules of cytochrome c at low ionic strength

et al. 2015

View full text Add to dashboard Cite

show abstract

“…4A and 4B). It has been reported that caspase-3 amplifies Cytc release and mitochondria fragmentation by cleaving CYC1 during mitochondria-dependent apoptosis [11]. In the mitochondrial electron transport chain, CYC1 directly interacts and stabilizes Cytc.…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, a recent study reported that CYC1 cleavage by caspase-3 disrupts mitochondrial function and enhances Cyt c release and apoptosis [11]. Thus, we speculated that CYC1 downregulation in OS might sensitize OS cells to apoptotic induction by TRAIL through promoting Cyt c release.…”

Section: Introductionmentioning

confidence: 97%

CYC1 Silencing Sensitizes Osteosarcoma Cells to TRAIL-Induced Apoptosis

Liang

et al. 2014

Cell Physiol Biochem

View full text Add to dashboard Cite

Aims: Osteosarcoma (OS) is an aggressive bone malignancy with poor prognosis. Many OS cells are resistant to apoptotic induction by tumor necrosis factor-related apoptosis inducing ligand (TRAIL). In our previous study, we found that the serum level of cytochrome c1 (CYC1) is significantly higher in OS patients than in healthy subjects. Our aim was to investigate the effects of CYC1 silencing on TRAIL-induced apoptosis in human OS in vitro and in vivo along with the underlying mechanisms. Methods: First, we determined the expression of CYC1 in human OS tumors and cell lines versus normal adjacent tissues and cell line. We then studied the effects of CYC1 silencing alone or in combination with TRAIL on OS cell growth and apoptosis in vitro and OS tumorigenesis in vivo. Results: We found that CYC1 is overexpressed in human OS tissues and cell lines. CYC1 silencing by shRNA transfection inhibits proliferation, slightly induces apoptosis in human OS cells in vitro, and suppresses human OS tumor growth in a mouse xenograft model in vivo. Additionally, CYC1 silencing sensitizes OS to TRAIL-induced apoptosis in vitro and in vivo. Our results also showed that CYC1 silencing significantly reduces complex III activity and potentiates TRAIL-induced cytochrome c release and caspase-9 activation in OS cells, suggesting that CYC1 silencing acts via the mitochondria-dependent apoptotic pathway. Conclusion: Taken together, our results provide evidence that CYC1 plays an important role in OS tumorigenesis, and modulation of CYC1 may be an effective strategy to potentiate OS to apoptotic induction by TRAIL.

show abstract

“…The other pro-apoptotic or antiproliferative protein genes downregulated were DAPK3 (Kawai et al, 1998), BMF (Puthalakath et al, 2001), RBL2 (Dick, 2007), RBBP2 (Chicas et al, 2012), BNIP3 (Burton et al, 2013), APP (Takahashi et al, 2009) Table S2). Similarly, anti-apoptotic/cell proliferation genes downregulated are CACNB4 (Tadmouri et al, 2012), TNFRSF11B (Oliver et al, 2013), CAPN6 (Rho et al, 2008), GRB2 (Kraskouskaya et al, 2013), TRAF6 (Wong et al, 1999), BZRP (Maaser et al, 2002), TNFRSF6B (Chen et al, 2010), RAF1 (McPhillips et al, 2006), CYC1 (Zhu et al, 2012), and HSPD1 (Ghosh et al, 2008) (Supplementary Table S2). …”

Section: Discussionmentioning

confidence: 99%

Repurposing L-Menthol for Systems Medicine and Cancer Therapeutics? L-Menthol Induces Apoptosis through Caspase 10 and by Suppressing HSP90

Faridi

Dhawan

Pal

et al. 2016

OMICS: A Journal of Integrative Biology

View full text Add to dashboard Cite

The objective of the present study was to repurpose L-menthol, which is frequently used in oral health and topical formulations, for cancer therapeutics. In this article, we argue that monoterpenes such as L-menthol might offer veritable potentials in systems medicine, for example, as cheaper anti-cancer compounds. Other monoterpenes such as limonene, perillyl alcohol, and geraniol have been shown to induce apoptosis in various cancer cell lines, but their mechanisms of action are yet to be completely elucidated. Earlier, we showed that L-menthol modulates tubulin polymerization and apoptosis to inhibit cancer cell proliferation. In the present report, we used an apoptosis-related gene microarray in conjunction with proteomics analyses, as well as in silico interpretations, to study gene expression modulation in human adenocarcinoma Caco-2 cell line in response to L-menthol treatment. The microarray analysis identified caspase 10 as the important initiator caspase, instead of caspase 8. The proteomics analyses showed downregulation of HSP90 protein (also corroborated by its low transcript abundance), which in turn indicated inhibition of AKT-mediated survival pathway, release of pro-apoptotic factor BAD from BAD and BCLxL complex, besides regulation of other factors related to apoptosis. Based on the combined microarray, proteomics, and in silico data, a signaling pathway for L-menthol-induced apoptosis is being presented for the first time here. These data and literature analysis have significant implications for ''repurposing'' L-menthol beyond oral medicine, and in understanding the mode of action of plant-derived monoterpenes towards development of cheaper anticancer drugs in future.

show abstract

Caspase cleavage of cytochrome c1 disrupts mitochondrial function and enhances cytochrome c release

Cited by 44 publications

References 48 publications

Respiratory complexes III and IV can each bind two molecules of cytochrome c at low ionic strength

Respiratory complexes III and IV can each bind two molecules of cytochrome c at low ionic strength

CYC1 Silencing Sensitizes Osteosarcoma Cells to TRAIL-Induced Apoptosis

Repurposing L-Menthol for Systems Medicine and Cancer Therapeutics? L-Menthol Induces Apoptosis through Caspase 10 and by Suppressing HSP90

Contact Info

Product

Resources

About