共查询到20条相似文献,搜索用时 31 毫秒
1.
Yide Mei Jeongsik Yong Aaron Stonestrom Xiaolu Yang 《Cell cycle (Georgetown, Tex.)》2010,9(15):2936-2939
Both transfer RNA (tRNA) and cytochrome c are essential to cellular function: tRNA mediates protein synthesis while cytochrome c is required for oxidative phosphorylation and apoptosis induction. tRNA has recently been implicated as a direct regulator of the well-conserved apoptotic role of cytochrome c. Interaction between these molecules could potentially coordinate biosynthesis, energy production and apoptosis. Here we review the diversity and dynamics of tRNA and how this class of non-coding RNAs may regulate the role of cytochrome c in apoptosis. We comment on unanswered questions in the cell biology of this interaction and how answers may influence our understanding of disease.Key words: tRNA, cytochrome c, apoptosis, caspase, mitochondria, protein synthesis, cancer 相似文献
2.
Madhavi Gorla Naresh Babu V. Sepuri 《Apoptosis : an international journal on programmed cell death》2014,19(1):259-268
In response to apoptotic stimuli, cytochrome c, an inter-membrane space protein is released from mitochondria to activate the cascade of caspases that leads to apoptosis. Recent evidence suggests that cytochrome c interacts with tRNA in the cytoplasm and this interaction was shown to inhibit the caspase mediated apoptotic process. Interestingly, cytochrome c does not contain any putative RNA binding domain. In this report, we sought to define the structural component of cytochrome c that is involved in binding of tRNA. By using gel mobility shift assays, we show that holocytochrome c can interact with tRNA but not apocytochrome c that lacks the heme domain suggesting that heme is essential for the interaction of cytochrome c to tRNA. In addition, using in vitro cross linking and circular dichroism spectroscopic studies, we show that cytochrome c can undergo heme mediated oligomerization. Prevention of heme mediated oligomerization of cytochrome c by potassium ferricyanide treatment prevents the binding of tRNA and promotes caspase activation. Our studies provide a novel regulation of apoptosis by heme dependent tRNA interaction to cytochrome c. 相似文献
3.
Cione E Tucci P Senatore V Perri M Trombino S Iemma F Picci N Genchi G 《Journal of bioenergetics and biomembranes》2008,40(1):19-26
Ferulic acid plays a chemopreventive role in cancer by inducing tumor cells apoptosis. As mitochondria play a key role in
the induction of apoptosis in many cells types, here we investigate the mitochondrial permeability transition (MPT) and the
release of cytochrome c induced by ferulic acid and its esters in rat testes mitochondria, in TM-3 and MLTC-1 cells. While ferulic acid, but not
its esters, induced MPT and cytochrome c release in rat testes isolated mitochondria, in TM-3 cells we found that both ferulic acid and its esters induced cytochrome
c release from mitochondria in a dose-dependent manner, suggesting a potential target of these compounds in the induction of
cell apoptosis. The apoptosis induced by ferulic acid is therefore associated with the mitochondrial pathway involving cytochrome
c release and caspase-3 activation.
Cione and Tucci have equally contributed to this article. 相似文献
4.
《Free radical research》2013,47(4):439-444
AbstractThe peroxidase-type reactivity of cytochrome c is proposed to play a role in free radical production and/or apoptosis. This study describes cytochrome c catalysis of peroxide consumption by ascorbate. Under conditions where the sixth coordination position at the cytochrome c heme iron becomes more accessible for exogenous ligands (by carboxymethylation, cardiolipin addition or by partial denaturation with guanidinium hydrochloride) this peroxidase activity is enhanced. A reaction intermediate is detected by stopped-flow UV-vis spectroscopy upon reaction of guanidine-treated cytochrome c with peroxide, which resembles the spectrum of globin Compound II species and is thus proposed to be a ferryl species. The ability of physiological levels of ascorbate (10–60 µM) to interact with this species may have implications for mechanisms of cell signalling or damage that are based on cytochrome c/peroxide interactions. 相似文献
5.
Oursler MJ Bradley EW Elfering SL Giulivi C 《American journal of physiology. Cell physiology》2005,288(1):C156-C168
Two unresolved aspects of the role of mitochondria-derived cytochrome c in apoptosis are whether there is a separate pool of cytochrome c within mitochondria that participates in the activation of apoptosis and whether a chemically modified cytochrome c drives apoptosis. These questions were investigated using osteoclasts, because they are rich in mitochondria and because osteoclast apoptosis is critical in bone metabolism regulation. H2O2 production was increased during culture, preceding cytochrome c release; both processes occurred anterior to apoptosis. With the addition of a mitochondrial uncoupler, H2O2 production and apoptosis were blocked, indicating the prominent role of mitochondria-derived H2O2. Trapping H2O2-derived hydroxyl radical decreased apoptosis. Cytosolic cytochrome c was originated from a single mitochondrial compartment, supporting a common pool involved in respiration and apoptosis, and it was chemically identical to the native form, with no indication of oxidative or nitrative modifications. Protein levels of Bcl-2 and Bc-xL were decreased before apoptosis, whereas expression of wild-type Bcl-2 repressed apoptosis, confirming that cytochrome c release is critical in initiating apoptosis. Cytosolic cytochrome c participated in activating caspase-3 and -9, both required for apoptosis. Collectively, our data indicate that the mitochondria-dependent apoptotic pathway is one of the major routes operating in osteoclasts. reactive oxygen species; nitric oxide; free radicals; caspase 相似文献
6.
W Abbas K A Khan A Kumar M K Tripathy I Dichamp M Keita U Mahlknecht O Rohr G Herbein 《Cell death & disease》2014,5(2):e1080
HIV-1 Nef protein has key roles at almost all stages of the viral life cycle. We assessed the role of Nef and of the translation elongation factor eEF1A in primary human macrophages. Nuclear retention experiments and inhibition of the exportin-t (Exp-t) pathway suggested that cytoplasmic relocalization of eEF1A, mediated by Exp-t occurs in Nef-treated monocyte-derived macrophages (MDMs). We observed the presence of tRNA in the Nef/eEF1A complexes. Nucleocytoplasmic relocalization of the Nef/eEF1A complexes prevented stress-induced apoptosis of MDMs treated with brefeldin A. Blockade of stress-induced apoptosis of MDMs treated with HIV-1 Nef resulted from enhanced nucleocytoplasmic transport of eEF1A with decreased release of mitochondrial cytochrome c, and from increased tRNA binding to cytochrome c, ultimately leading to an inhibition of caspase activation. Our results indicate that HIV-1 Nef, through the nucleocytoplasmic relocalization of eEF1A and tRNAs, enhances resistance to stress-induced apoptosis in primary human macrophages. 相似文献
7.
Rapak A Stasik I Ziolo E Strzadala L 《Apoptosis : an international journal on programmed cell death》2007,12(10):1873-1878
Nur77 is reported to undergo translocation to mitochondria in response to apoptotic signaling in a variety of cancer cell
lines. It was shown that on the mitochondrial membrane, Nur77 interacts with Bcl-2, leading to the conversion of this protein
from a protector to a killer with subsequent release of cytochrome c to the cytosol. Here it is shown that in thymic lymphoma cells resistant to calcium-mediated apoptosis, cytochrome c release is abolished despite of Nur77 mitochondrial targeting. However, cytochrome c release and apoptosis can be restored by treatment with FK506. Hence, the molecular target regulation of the sensitivity
of lymphoma cells to calcium signaling is associated with cytochrome c release and is FK506 sensitive. These results provide new insight into the role of FK506-sensitive factors as a critical
link between calcium signaling and resistance of lymphoma cells to death. 相似文献
8.
Maria Piqu Montserrat Barragn Mireia Dalmau Beatriz Bellosillo Gabriel Pons Joan Gil 《FEBS letters》2000,480(2-3)
Aspirin and other non-steroidal anti-inflammatory drugs induce apoptosis in many cell types. Although the involvement of caspases has been demonstrated, the mechanism leading to caspase activation remains unknown. We have studied the role of the mitochondrial pathway in aspirin-induced apoptosis. The apoptotic effect of aspirin was analyzed in different cell lines (Jurkat, MOLT-4, Raji and HL-60) showing induction of mitochondrial cytochrome c release and caspases 9, 3 and 8 processing. Furthermore, early aspirin-induced cytochrome c release was not affected by the caspase inhibitor Z-VAD·fmk and preceded loss of mitochondrial membrane potential. Therefore, aspirin-induced apoptosis involves caspase activation through cytochrome c release. 相似文献
9.
Cytochrome c is a heme protein involved in electron transfer, cell apoptosis, and diseases associated with oxidative stress. Here we expressed human cytochrome c in E. coli and purified it to homogeneity with a yield of 10–15 mg/L. The redox potential of recombinant human cytochrome c was 0.246 V which was measured by cyclic voltammetry. This is similar to that of horse cytochrome c with a value of 0.249 V. The sequential assignment and structural analysis of recombinant human ferrocytochrome c were obtained using multidimensional NMR spectroscopy. On the basis of our NMR studies, the recombinant human cytochrome c produced in E. coli exhibits the same tertiary fold as horse cytochrome c. These results provide evidence that human cytochrome c expressed in E. coli possesses a similar function and structure to that of the horse protein. It is known that cytochrome c plays a role in many human diseases. This study serves as the basis for gaining insight into human diseases by exploring structure and function relationships of cytochrome c to its interacting proteins. 相似文献
10.
Mitochondria play a pivotal role in the regulation of apoptosis. An imbalance in apoptosis can lead to disease. Unscheduled apoptosis has been linked to neurodegeneration while inhibition of apoptosis can cause cancer. An early and key event during apoptosis is the release of factors from mitochondria. In apoptosis the mitochondrial outer membrane becomes permeable, leading to release of apoptogenic factors into the cytosol. One such factor, cytochrome c, is an electron carrier of the respiratory chain normally trapped within the mitochondrial intermembrane space. Many apoptotic studies investigate mitochondrial outer membrane permeabilization (MOMP) by monitoring the release of cytochrome c. Here, we describe three reliable techniques that detect cytochrome c release from mitochondria, through subcellular fractionation or immunocytochemistry and fluorescence microscopy, or isolated mitochondria and recombinant Bax and t-Bid proteins in vitro. These techniques will help to identify mechanisms and characterize factors regulating MOMP. 相似文献
11.
W Abbas K A Khan M K Tripathy I Dichamp M Keita O Rohr G Herbein 《Cell death & disease》2012,3(4):e292
HIV-1 Nef protein has key roles at almost all stages of the viral life cycle. We assessed the role of the Nef/eEF1A (eukaryotic translation elongation factor 1-alpha) complex in nucleocytoplasmic shuttling in primary human macrophages. Nuclear retention experiments and inhibition of the exportin-t (Exp-t) pathway suggested that cytoplasmic relocalization of eEF1A, mediated by Exp-t, occurs in Nef-treated monocyte-derived macrophages (MDMs). We observed the presence of tRNA in the Nef/eEF1A complexes. Nucleocytoplasmic relocalization of the Nef/eEF1A complexes prevented stress-induced apoptosis of MDMs treated with brefeldin-A. Blockade of stress-induced apoptosis of MDMs treated with HIV-1 Nef resulted from enhanced nucleocytoplasmic transport of eEF1A with decreased release of mitochondrial cytochrome c, and from increased tRNA binding to cytochrome c, ultimately leading to an inhibition of caspase activation. Our results indicate that HIV-1 Nef, through the nucleocytoplasmic relocalization of eEF1A and tRNAs, enhances resistance to stress-induced apoptosis in primary human macrophages. 相似文献
12.
Rodríguez-Hernández A Brea-Calvo G Fernández-Ayala DJ Cordero M Navas P Sánchez-Alcázar JA 《Apoptosis : an international journal on programmed cell death》2006,11(1):131-139
Chemotherapy-induced apoptosis by DNA-damaging drugs is thought to be generally dependent on the release of cytochrome c and the subsequent activation of caspase-9 and -3. However, the molecular mechanism of how damaged DNA triggers the apoptotic
process is not clear. To better understand the mechanisms underlying this process, we examined drug-induced apoptosis in cultured
H-460 cells. Using cell fractionation, western blotting, and immunofluorescence assays, we show that the activation of nuclear
caspases-7 and -3, and poly(ADP-ribose) polymerase (PARP) cleavage, are early events in camptothecin-induced apoptosis. Moreover,
we demonstrate that these events precede the release of cytochrome c and apoptotic inducing factor, and the activation of caspases 2, 8, 9 and 12. Together our results suggest that drugs acting
at the DNA level can initiate apoptosis via nuclear caspase activation.
An erratum to this article is available at . 相似文献
13.
14.
Mitochondria,oxidative stress and cell death 总被引:4,自引:0,他引:4
Ott M Gogvadze V Orrenius S Zhivotovsky B 《Apoptosis : an international journal on programmed cell death》2007,12(5):913-922
In addition to the well-established role of the mitochondria in energy metabolism, regulation of cell death has recently emerged
as a second major function of these organelles. This, in turn, seems to be intimately linked to their role as the major intracellular
source of reactive oxygen species (ROS), which are mainly generated at Complex I and III of the respiratory chain. Excessive
ROS production can lead to oxidation of macromolecules and has been implicated in mtDNA mutations, ageing, and cell death.
Mitochondria-generated ROS play an important role in the release of cytochrome c and other pro-apoptotic proteins, which can trigger caspase activation and apoptosis. Cytochrome c release occurs by a two-step process that is initiated by the dissociation of the hemoprotein from its binding to cardiolipin,
which anchors it to the inner mitochondrial membrane. Oxidation of cardiolipin reduces cytochrome c binding and results in an increased level of “free” cytochrome c in the intermembrane space. Conversely, mitochondrial antioxidant enzymes protect from apoptosis. Hence, there is accumulating
evidence supporting a direct link between mitochondria, oxidative stress and cell death. 相似文献
15.
Cardiolipin: Setting the beat of apoptosis 总被引:4,自引:0,他引:4
Gonzalvez F Gottlieb E 《Apoptosis : an international journal on programmed cell death》2007,12(5):877-885
Cardiolipin (CL) is a mitochondria-specific phospholipid which is known to be intimately linked with the mitochondrial bioenergetic
machinery. Accumulating evidence now suggests that this unique lipid also has active roles in several of the mitochondria-dependant
steps of apoptosis. CL is closely associated with cytochrome c at the outer leaflet of the mitochondrial inner membrane. This interaction makes the process of cytochrome c release from mitochondria more complex than previously assumed, requiring more than pore formation in the mitochondrial outer
membrane. While CL peroxidation could be crucial for enabling cytochrome c dissociation from the mitochondrial inner membrane, cytochrome c itself catalyzes CL peroxidation. Moreover, peroxy-CL directly activates the release of cytochrome c and other apoptogenic factors from the mitochondria. CL is also directly involved in mitochondrial outer membrane permeabilization
by enabling docking and activation of pro-apoptotic Bcl-2 proteins. It appears therefore that CL has multiple roles in apoptosis
and that CL metabolism contributes to the complexity of the apoptotic process. 相似文献
16.
Carlos A. Elena-Real Katiuska González-Arzola Gonzalo Pérez-Mejías Antonio Díaz-Quintana Adrián Velázquez-Campoy Bénédicte Desvoyes Crisanto Gutiérrez Miguel A. De la Rosa Irene Díaz-Moreno 《The Plant journal : for cell and molecular biology》2021,106(1):74-85
Programmed cell death (PCD) is crucial for development and homeostasis of all multicellular organisms. In human cells, the double role of extra-mitochondrial cytochrome c in triggering apoptosis and inhibiting survival pathways is well reported. In plants, however, the specific role of cytochrome c upon release from the mitochondria remains in part veiled yet death stimuli do trigger cytochrome c translocation as well. Here, we identify an Arabidopsis thaliana 14-3-3ι isoform as a cytosolic cytochrome c target and inhibitor of caspase-like activity. This finding establishes the 14-3-3ι protein as a relevant factor at the onset of plant H2O2-induced PCD. The in vivo and in vitro studies herein reported reveal that the interaction between cytochrome c and 14-3-3ι exhibits noticeable similarities with the complex formed by their human orthologues. Further analysis of the heterologous complexes between human and plant cytochrome c with plant 14-3-3ι and human 14-3-3ε isoforms corroborated common features. These results suggest that cytochrome c blocks p14-3-3ι so as to inhibit caspase-like proteases, which in turn promote cell death upon H2O2 treatment. Besides establishing common biochemical features between human and plant PCD, this work sheds light onto the signaling networks of plant cell death. 相似文献
17.
Jan-Willem Taanman 《Journal of bioenergetics and biomembranes》1997,29(2):151-163
As the terminal component of the mitochondrial respiratory chain, cytochrome c oxidase plays a vital role in cellular energy transformation. Human cytochrome c oxidase is composed of 13 subunits. The three major subunits form the catalytic core and are encoded by mitochondrial DNA (mtDNA). The remaining subunits are nuclear-encoded. The primary sequence is known for all human subunits and the crystal structure of bovine heart cytochrome c oxidase has recently been reported. However, despite this wealth of structural information, the role of the nuclear-encoded subunits is still poorly understood. Yeast cytochrome c oxidase is a close model of its human counterpart and provides a means of studying the effects of mutations on the assembly, structure, stability and function of the enzyme complex. Defects in cytochrome c oxidase function are found in a clinically heterogeneous group of disorders. The molecular defects that underlie these diseases may arise from mutations of either the mitochondrial or the nuclear genomes or both. A significant number of cytochrome c oxidase deficiencies, often associated with other respiratory chain enzyme defects, are attributed to mutations of mtDNA. Mutations of mtDNA appear, nonetheless, uncommon in early childhood. Pedigree analysis and cell fusion experiments have demonstrated a nuclear involvement in some infantile cases but a specific nuclear genomic lesion has not yet been reported. Detailed analyses of the many steps involved in the biogenesis of cytochrome c oxidase, often pioneered in yeast, offer several starting points for further molecular characterizations of cytochrome c oxidase deficiencies observed in clinical practice. 相似文献
18.
Mitochondria play an important role in the progression of apoptosis through the release of pro-apoptotic factors, such as cytochrome c, from the mitochondrial intermembrane space. During this process, mitochondrial networks are dramatically reorganised from long filamentous interconnected tubules into small punctate spheres. Whether remodelling of mitochondrial networks is necessary for apoptosis-associated cytochrome c release, or merely an accompanying process, has been a subject of debate. Here we discuss evidence for and against the role of mitochondrial fragmentation in the progression of apoptosis and highlight recent advances which indicate that mitochondrial fission is not a critical requirement for apoptosis-associated cytochrome c release. We also discuss an emerging role for Bcl-2 family members as regulators of mitochondrial fission and fusion dynamics, independent of the role of this family in the regulation of apoptosis. 相似文献
19.
Furre IE Møller MT Shahzidi S Nesland JM Peng Q 《Apoptosis : an international journal on programmed cell death》2006,11(11):2031-2042
Photodynamic therapy (PDT) is a cancer treatment based on the interaction of a photosensitizer, light and oxygen. PDT with
the endogenous photosensitizer, protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (ALA) or its derivatives is a modification
of this treatment modality with successful application in dermatology. However, the mechanism of cell destruction by ALA-PDT
has not been elucidated. In this study a human T-cell lymphoma Jurkat cell line was treated with PDT using hexaminolevulinate
(HAL, hexylester of ALA). Four hours following treatment nearly 80% of the cells exhibited typical apoptotic features. Mitochondrial
pro-apoptotic proteins were evaluated by Western blots in subcellular fractionated samples. PDT caused cytosolic translocation
of cytochrome c and nuclear redistribution of apoptosis-inducing factor (AIF), but the release of mitochondrial Smac/DIABLO, Omi/HtrA2 and
EndoG was not observed. The release of cytochrome c was followed by the cleavage of caspase-9 and caspase-3 as well as its downstream substrates, together with oligonucleosomal
DNA fragmentation. The pan-caspases inhibitor, z-VAD.fmk, prevented oligonucleosomal DNA fragmentation, but failed to inhibit
PDT-mediated apoptosis. The apoptotic induction by AIF-mediated caspase-independent pathway was also found after HAL-PDT with
large-scale DNA fragmentation in the presence of z-VAD.fmk. These results demonstrate that cytochrome c-mediated caspase-dependent pathway and AIF-induced caspase-independent pathway are simultaneously involved in the apoptotic
induction by PDT. When the cytochrome c-induced caspase-dependent pathway is blocked, the cells go into apoptosis via AIF-mediated pathway, clearly demonstrating
that the cytochrome c-mediated caspase-dependent pathway is not required for such apoptotic induction. This finding may have an impact on improved
PDT effectiveness. 相似文献
20.
Shiva Akbari-Birgani Saman Hosseinkhani Sepideh Mollamohamadi Hossein Baharvand 《The Journal of biological chemistry》2014,289(24):16905-16913
Differentiation is an inseparable process of development in multicellular organisms. Mouse embryonic stem cells (mESCs) represent a valuable research tool to conduct in vitro studies of cell differentiation. Apoptosis as a well known cell death mechanism shows some common features with cell differentiation, which has caused a number of ambiguities in the field. The research question here is how cells could differentiate these two processes from each other. We have investigated the role of the mitochondrial apoptotic pathway and cell energy level during differentiation of mESCs into the cardiomyocytes and their apoptosis. p53 expression, cytochrome c release, apoptosome formation, and caspase-3/7 activation are observed upon induction of both apoptosis and differentiation. However, remarkable differences are detected in time of cytochrome c appearance, apoptosome formation, and caspase activity upon induction of both processes. In apoptosis, apoptosome formation and caspase activity were observed rapidly following the cytochrome c release. Unlike apoptosis, the release of cytochrome c upon differentiation took more time, and the maximum caspase activity was also postponed for 24 h. This delay suggests that there is a regulatory mechanism during differentiation of mESCs into cardiomyocytes. The highest ATP content of cells was observed immediately after cytochrome c release 6 h after apoptosis induction and then decreased, but it was gradually increased up to 48 h after differentiation. These observations suggest that a delay in the release of cytochrome c or delay in ATP increase attenuate apoptosome formation, and caspase activation thereby discriminates apoptosis from differentiation in mESCs. 相似文献