Citreoviridin, a specific inhibitor of the mitochondiral adenosine triphosphatase

Linnett, Paul E.; Mitchell, A. D.; Osselton, M. David; Mulheirn, L. J.; Beechey, R. B.

doi:10.1042/bj1700503

Cited by 51 publications

(26 citation statements)

References 29 publications

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“…Citreoviridin fluoresces weakly at 530 nm when irradiated at 380 nm. However, unlike aurovertin, enhancement is not observed when bound to F 1 (233 …”

Section: Polyenic ␣-Pyrone Derivativesmentioning

confidence: 97%

ATP Synthase and the Actions of Inhibitors Utilized To Study Its Roles in Human Health, Disease, and Other Scientific Areas

Hong

Pedersen

2008

Microbiol Mol Biol Rev

275

302

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SUMMARY ATP synthase, a double-motor enzyme, plays various roles in the cell, participating not only in ATP synthesis but in ATP hydrolysis-dependent processes and in the regulation of a proton gradient across some membrane-dependent systems. Recent studies of ATP synthase as a potential molecular target for the treatment of some human diseases have displayed promising results, and this enzyme is now emerging as an attractive molecular target for the development of new therapies for a variety of diseases. Significantly, ATP synthase, because of its complex structure, is inhibited by a number of different inhibitors and provides diverse possibilities in the development of new ATP synthase-directed agents. In this review, we classify over 250 natural and synthetic inhibitors of ATP synthase reported to date and present their inhibitory sites and their known or proposed modes of action. The rich source of ATP synthase inhibitors and their known or purported sites of action presented in this review should provide valuable insights into their applications as potential scaffolds for new therapeutics for human and animal diseases as well as for the discovery of new pesticides and herbicides to help protect the world's food supply. Finally, as ATP synthase is now known to consist of two unique nanomotors involved in making ATP from ADP and Pi, the information provided in this review may greatly assist those investigators entering the emerging field of nanotechnology.

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“…Citreoviridin fluoresces weakly at 530 nm when irradiated at 380 nm. However, unlike aurovertin, enhancement is not observed when bound to F 1 (233 …”

Section: Polyenic ␣-Pyrone Derivativesmentioning

confidence: 97%

ATP Synthase and the Actions of Inhibitors Utilized To Study Its Roles in Human Health, Disease, and Other Scientific Areas

Hong

Pedersen

2008

Microbiol Mol Biol Rev

275

302

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“…Specifically, we used a proteomics approach and constructed a protein-protein interaction (PPI) network, to investigate the role of tumor ectopic ATP synthase and the effects of its inhibitor citreoviridin, which exhibits specific inhibition on F 1 F 0 ATP synthase (18,19).…”

Section: Unlike In Normal Cells Its Function In Tumor Cellsmentioning

confidence: 99%

Ectopic ATP Synthase Blockade Suppresses Lung Adenocarcinoma Growth by Activating the Unfolded Protein Response

Chang

Huang

et al. 2012

Cancer Research

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Ectopic expression of the mitochondrial F 1 F 0 -ATP synthase on the plasma membrane has been reported to occur in cancer, but whether it exerts a functional role in this setting remains unclear. Here we show that ectopic ATP synthase and the electron transfer chain exist on the plasma membrane in a punctuated distribution of lung adenocarcinoma cells, where it is critical to support cancer cell proliferation. Applying ATP synthase inhibitor citreoviridin induced cell cycle arrest and inhibited proliferation and anchorage-independent growth of lung cancer cells. Analysis of protein expression profiles after citreoviridin treatment suggested this compound induced the unfolded protein response (UPR) associated with phosphorylation the translation initiation factor 2a (eIF2a), triggering cell growth inhibition. Citreoviridin-enhanced eIF2a phosphorylation could be reversed by siRNA-mediated attenuation of the UPR kinase PKR-like endoplasmic reticulum kinase (PERK) combined with treatment with the antioxidant N-acetylcysteine, establishing that reactive oxygen species (ROS) boost UPR after citreoviridin treatment. Thus, a coordinate elevation of UPR and ROS initiates a positive feedback loop that convergently blocks cell proliferation. Our findings define a molecular function for ectopic ATP synthase at the plasma membrane in lung cancer cells and they prompt further study of its inhibition as a potential therapeutic approach. Cancer Res; 72(18); 4696-706. Ó2012 AACR.

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“…The resolution of the instrument was set to 60000 at m/z 400 with an automated gain control (AGC) value of 10 6 . The top ten most-intense precursor ions were selected from the MS 1 The abbreviations used are: MAPK, mitogen-activated protein kinase; ATP, adenosine triphosphate; ecto-ATP synthase ectopic ATP, synthase; HSP90AB1, heat shock protein 90 ␤; Akt, serine/ threonine protein kinase; DMSO, dimethyl sulfoxide; HAMMOC, hydroxy acid-modified metal oxide chromatography; Ser, serine; Thr, threonine; Tyr, tyrosine; CK2, casein kinase 2; CSNK2A1, casein kinase 2 alpha; CSNK2A2, casein kinase 2 alpha isoform; CDK, cyclin-dependent kinase; HSPH1, heat shock protein 105 kDa; EP300, histone acetyltransferase p300; LMNB1, lamin-B1; LEMD3, inner nuclear membrane protein Man1; TMPO, lamina-associated polypeptide 2; NPM1, nucleoplasmin; HDAC1, histone deacetylase 1; USP2, ubiquitin carboxyl-terminal hydrolase 2; LEO1, RNA polymerase-associated; DSCAM, Down syndrome cell adhesion molecule; ST13, hsc70-interacting protein; ERK, extracellular signal-regulated kinase; Raf-1, RAF proto-oncogene serine/threonine-protein kinase; MEK, dual specificity mitogen-activated protein kinase; 2DE, twodimensional gel electrophoresis; TEAB, triethylammonium bicarbonate; PWM, position weight matrix; AGC, automatic gain control; PCR, polymerase chain reaction. scan for subsequent collision-induced dissociation MS/MS scan by ion trap (AGC target at 7000).…”

Section: Methodsmentioning

confidence: 99%

“…Many protein kinases such as mitogen-activated protein kinases (MAPKs) 1 and serine/threonine protein kinase (Akt) are major enzymes that drive tumor growth by signal transduction, leading to transcriptional changes of oncogenes (23,24). Therefore, characterization of protein phosphorylation status following stimuli-induced signaling changes may provide important insight into the regulation of physiological events in cells.…”

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confidence: 99%

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Temporal Phosphoproteome Dynamics Induced by an ATP Synthase Inhibitor Citreoviridin*

Hsu

Wang³

et al. 2015

Molecular & Cellular Proteomics

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Citreoviridin, one of toxic mycotoxins derived from fungal species, can suppress lung cancer cell growth by inhibiting the activity of ectopic ATP synthase, but has limited effect on normal cells. However, the mechanism of citreoviridin triggering dynamic molecular responses in cancer cells remains unclear. Here, we performed temporal phosphoproteomics to elucidate the dynamic changes after citreoviridin treatment in cells and xenograft model. We identified a total of 829 phosphoproteins and demonstrated that citreoviridin treatment affects protein folding, cell cycle, and cytoskeleton function. Furthermore, response network constructed by mathematical modeling shows the relationship between the phosphorylated heat shock protein 90 β and mitogen-activated protein kinase signaling pathway. This work describes that citreoviridin suppresses cancer cell growth and mitogenactivated protein kinase/extracellular signal-regulated kinase signaling by site-specific dephosphorylation of HSP90AB1 on Serine 255 and provides perspectives in cancer therapeutic strategies. Molecular & Cellular

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Citreoviridin, a specific inhibitor of the mitochondiral adenosine triphosphatase

Cited by 51 publications

References 29 publications

ATP Synthase and the Actions of Inhibitors Utilized To Study Its Roles in Human Health, Disease, and Other Scientific Areas

ATP Synthase and the Actions of Inhibitors Utilized To Study Its Roles in Human Health, Disease, and Other Scientific Areas

Ectopic ATP Synthase Blockade Suppresses Lung Adenocarcinoma Growth by Activating the Unfolded Protein Response

Temporal Phosphoproteome Dynamics Induced by an ATP Synthase Inhibitor Citreoviridin*

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