Mitochondrial membrane remodeling in apoptosis: an inside story

Delivani, Petrina; Martin, Séamus J.

doi:10.1038/sj.cdd.4402049

Cited by 37 publications

(42 citation statements)

References 21 publications

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“…Notably, ϳ90% of mitochondrial Cc content is sequestered within the cristae of the inner membrane and therefore is unavailable for electron transport (10). Moreover, the interaction of Cc with Apaf-1, leading to apoptosome formation, is one of the earliest events to occur at the onset of apoptosis, a process requiring small amounts of the heme protein because of the amplification of its effect by the proteolytic cascade.…”

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confidence: 99%

Structural and Functional Analysis of Novel Human Cytochrome c Targets in Apoptosis

Martínez-Fábregas

Dı́az-Moreno

González‐Arzola

et al. 2014

Molecular & Cellular Proteomics

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Since the first description of apoptosis four decades ago, great efforts have been made to elucidate, both in vivo and in vitro, the molecular mechanisms involved in its regulation. Although the role of cytochrome c during apoptosis is well established, relatively little is known about its participation in signaling pathways in vivo due to its essential role during respiration. To obtain a better understanding of the role of cytochrome c in the onset of apoptosis, we used a proteomic approach based on affinity chromatography with cytochrome c as bait in this study. In this approach, novel cytochrome c interaction partners were identified whose in vivo interaction and cellular localization were facilitated through bimolecular fluorescence complementation. Modeling of the complex interface between cytochrome c and its counterparts indicated the involvement of the surface surrounding the heme crevice of cytochrome c, in agreement with the vast majority of known redox adducts of cytochrome c. However, in contrast to the high turnover rate of the mitochondrial cytochrome c redox adducts, those occurring under apoptosis led to the formation of stable nucleo-cytoplasmic ensembles, as inferred mainly from surface plasmon resonance and nuclear magnetic resonance measurements, which permitted us to corroborate the formation of such complexes in vitro. The results obtained suggest that human cytochrome c interacts with pro-survival, anti-apoptotic proteins following its release into the cytoplasm. Thus, cytochrome c may interfere with cell survival pathways and unlock apoptosis in order to prevent the spatial and temporal coexistence of antagonist signals. Molecular & Cellular

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confidence: 99%

Structural and Functional Analysis of Novel Human Cytochrome c Targets in Apoptosis

Martínez-Fábregas

Dı́az-Moreno

González‐Arzola

et al. 2014

Molecular & Cellular Proteomics

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“…Mitochondria play a critical role in apoptosis induced by chemotherapeutic agents [12][13][14] . Many agents can induce, directly or indirectly, apoptosis by insult to the mitochondria [34,35] .…”

Section: Discussionmentioning

confidence: 99%

“…Three apoptotic pathways have been addressed, including the mitochondrial pathway [12,13] , death receptor pathway [14] , and endoplasmic reticulum stress-mediated apoptosis pathway [15] . The mitochondrial pathway initiates apoptosis in most physiological and pathological situations.…”

Section: Introductionmentioning

confidence: 99%

“…Many agents can induce, directly or indirectly, apoptosis by insult to the mitochondria [34,35] . Apoptosis could cause loss of Δψm and release of cytochrome C into cytosol, and induce caspase-9-dependent activation of caspase-3 [13] . In this study, the effect of ESB on Δψm was examined using Rhodamine 123, a mitochondrial potential probe, showing that H22 cells lost Δψm following ESB treatment.…”

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confidence: 99%

“…Flow cytometry showed that cell apoptosis was significantly decreased at S-phase, increased at G 1 -phase, and reached its peak at subG 1 -phase. The blocking of cell cycle may be one of the mechanisms of ESB by which the growth of H22 cells is inhibited and cell apoptosis is induced.Mitochondria play a critical role in apoptosis induced by chemotherapeutic agents [12][13][14] . Many agents can induce, directly or indirectly, apoptosis by insult to the mitochondria [34,35] .…”

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Scutellaria barbate extract induces apoptosis of hepatoma H22 cells via the mitochondrial pathway involving caspase-3

Dai¹,

Wang²,

Li³

et al. 2008

WJG

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of cell cycle, the percentage of cells in S phase was significantly decreased, while the percentage of cells in G 1 phase was increased. Flow cytometry assay also showed that ESB had a positive effect on apoptosis. Typical apoptotic morphologies such as condensation and fragmentation of nuclei and blebbing membrane of apoptotic cells could be observed under transmission electron microscope and fluorescence microscope. To further investige the molecular mechanism behind ESB-induced apoptosis, ESB-treated cells rapidly lost their mitochondrial transmembrane potential, released mitochondrial cytochrome C into cytosol, and induced caspase-3 activity in a dose-dependent manner. CONCLUSION: ESB can effectively inhibit the proliferation and induce apoptosis of H22 cells involving loss of mitochondrial transmembrane potential, release of cytochrome C, and activation of caspase-3. INTRODUCTIONScutellaria barbata D.Don (S. barbata) is a perennial herb, also known as Ban-Zhi-Lian (barbat sskullcap) in traditional Chinese medicine. It is mainly distributed in southern China and has been used as an antitumor agent for lung cancer, digestive system cancer, hepatoma, breast cancer, and chorioepithelioma as well as an anti-inflammatory agent and a diuretic in China and Korea [1][2][3][4][5][6][7][8][9] . Extracts from S. barbata (ESB) have in vitro growth inhibitory effects on a number of human cancers including leukemia, colon cancer, hepatoma and skin cancer [4][5][6][7][8][9][10] . However, its antitumor mechanism still remains unclear.It was reported that many Chinese herbs have anticancer properties and induce apoptosis [11] . Three apoptotic pathways have been addressed, including the mitochondrial pathway [12,13] , death receptor pathway [14] , and endoplasmic reticulum stress-mediated apoptosis pathway [15] . The mitochondrial pathway initiates apoptosis in most physiological and pathological situations. Permeabilization outside mitochondrial membrane plays the most important role in mitochondrial apoptosis. In the mitochondria-initiated pathway, mitochondria undergoing permeability transition release apoptogenic proteins such as cytochrome C or apoptosis-inducing factor from the mitochondrial intermembrane space into the cytosol [16] . Released cytochrome C can activate caspase-9, and activated caspase-9 in turn cleaves and activates executioner caspase-3. After caspase-3 activation, some specific substrates for caspase-3 such as poly (ADP-ribose) and polymerase (PARP) are cleaved, and eventually lead to apoptosis [17] . In this study, S. barbata extract showed anti-tumor activity in vitro and could inhibit the growth of mouse H22 hepatoma cells by inhibiting cell apoptosis and cytotoxic effects, demonstrating that the extract from S. barbata can strongly inhibit cell proliferation and induce apoptosis of H22 cells through the mitochondrial dysfunction pathway. MATERIALS AND METHODSReagents and animals N e w b ov i n e s e r u m ( G i b c o, U S A ) , R P M I -1 6 4 0 medium(Gibco, USA), propidium iodide (PI) (Sigma, ...

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18β‐glycyrrhetinic acid induces apoptosis through modulation of Akt/FOXO3a/Bim pathway in human breast cancer MCF‐7 cells

Sharma

Kar

Palit

et al. 2012

Journal Cellular Physiology

112

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Triterpenes found in plants display a multitude of biological activities, including anti-tumor properties. The present study investigates the effect of 18β-glycyrrhetinic acid (GRA) a pentacyclic triterpenoid of the β-amyrin type, isolated from the root of Licorice (Glycyrrhizza glabra) on human breast cancer cells, MCF-7. GRA showed potent inhibitory effects on MCF-7 proliferation in a concentration- and time-dependent manner without affecting immortalized normal mammary epithelial cell line (MCF-10A). Growth inhibition of MCF-7 cells by GRA occurred through apoptosis, as evident from phosphatidyl serine externalization and DNA fragmentation. Apoptosis was primarily mediated through mitochondrial death cascade as evidenced by loss of mitochondrial membrane potential, release of cytochrome c and activation of caspase-9. GRA induced an increase in Bax:Bcl-2 ratio along with a significant increase in the protein level of the BH3 protein Bim. SiRNA-mediated knock down of Bim markedly attenuated GRA-mediated apoptosis. Profiling of transcriptional regulators of Bim revealed a role of Forkhead box O 3a transcription factor (FOXO3a) as judged by increased expression and nuclear translocation of FOXO3a. Silencing of FOXO3a resulted in marked attenuation in the expression of Bim as well as protection against GRA-mediated apoptosis. Furthermore, GRA-induced activation and nuclear localization of FOXO3a was associated with a reduced activity of Akt kinase. These results suggest that GRA induces apoptosis in human breast carcinoma MCF-7 cells via caspase activation and modulation of Akt/FOXO3a pathway.

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Mitochondrial membrane remodeling in apoptosis: an inside story

Cited by 37 publications

References 21 publications

Structural and Functional Analysis of Novel Human Cytochrome c Targets in Apoptosis

Structural and Functional Analysis of Novel Human Cytochrome c Targets in Apoptosis

Scutellaria barbate extract induces apoptosis of hepatoma H22 cells via the mitochondrial pathway involving caspase-3

18β‐glycyrrhetinic acid induces apoptosis through modulation of Akt/FOXO3a/Bim pathway in human breast cancer MCF‐7 cells

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