Molecular insights on cytochrome c and nucleotide regulation of apoptosome function and its implication in cancer

Yadav, Neelu; Gogada, Raghu; O’Malley, Jordan; Gundampati, Ravi Kumar; Jayanthi, Srinivas; Hashmi, Sana; Lella, Ravi K.; Zhang, Dianmu; Wang, Jianmin; Kumar, Rahul; Kumar, Thallapuranam Krishnaswamy Suresh; Chandra, Dhyan

doi:10.1016/j.bbamcr.2019.118573

Cited by 25 publications

(18 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The CARD is the binding module for procaspase-9, the NOD hosts a nucleotide binding site and mediates the oligomerization into the apoptosome, and the regulatory WD40-repeat domain serves as binding site for cytochrome c [ 10 ]. Both the activation and acting mode of Apaf-1 in the mammalian apoptosis signal pathway are well understood [ 11 ]. Briefly, Apaf-1 binds to cytochrome c, released from mitochondria, and dATP to form oligomeric apoptosome, which may induce caspase-9 dimerization and subsequent autocatalysis.…”

Section: Introductionmentioning

confidence: 99%

Identification and Functional Analysis of Apoptotic Protease Activating Factor-1 (Apaf-1) from Spodoptera litura

Yan

Lin

et al. 2021

Insects

View full text Add to dashboard Cite

Apoptotic protease activating factor-1 (Apaf-1) is an adaptor molecule, essential for activating initiator caspase and downstream effector caspases, which directly cause apoptosis. In fruit flies, nematodes, and mammals, Apaf-1 has been extensively studied. However, the structure and function of Apaf-1 in Lepidoptera remain unclear. This study identified a novel Apaf-1 from Spodoptera litura, named Sl-Apaf-1. Sl-Apaf-1 contains three domains: a CARD domain, as well as NOD and WD motifs, and is very similar to mammalian Apaf-1. Interference of Sl-apaf-1 expression in SL-1 cells blocked apoptosis induced by actinomycin D. Overexpression of Sl-apaf-1 significantly enhances apoptosis induced by actinomycin D in Sf9/SL-1/U2OS cells, suggesting that the function of Sl-Apaf-1 is evolutionarily conserved. Furthermore, Sl-Apaf-1 could interact with Sl-caspase-5 (a homologue of mammalian caspase-9) and yielded a binding affinity of 1.37 × 106 M–1 according isothermal titration calorimetry assay. Initiator caspase (procaspase-5) of S. litura could be activated by Sl-Apaf-1 (without WD motif) in vitro, and the activated Sl-caspase-5 could cleave Sl-procaspase-1 (a homologue of caspase-3 in mammals), which directly caused apoptosis. This study demonstrates the key role of Sl-Apaf-1 in the apoptosis pathway, suggesting that the apoptosis pathway in Lepidopteran insects and mammals is conserved.

show abstract

Section: Introductionmentioning

confidence: 99%

Identification and Functional Analysis of Apoptotic Protease Activating Factor-1 (Apaf-1) from Spodoptera litura

Yan

Lin

et al. 2021

Insects

View full text Add to dashboard Cite

show abstract

“…Cytc release forms an essential step in the apoptotic cascade, upon binding with apoptosis protease-activating factor 1 (Apaf-1), dATP, and procaspase-9 [ 24 , 25 ]. A number of studies have shown that Cytc can induce apoptosis of cancer cells [ 26 , 27 ]. Jamsheed et al [ 28 ] demonstrated that in non-small-cell lung cancer patients, Cytc level was lower than healthy individuals, and the lower expression of Cytc were associated with advanced stages, high grade histological differentiation, and shorter overall survival.…”

Section: Introductionmentioning

confidence: 99%

VDAC1 Conversely Correlates with Cytc Expression and Predicts Poor Prognosis in Human Breast Cancer Patients

Chen

Yin

Luo

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Aim. The main objective of this article was to evaluate the association of voltage-dependent anion channel 1 (VDAC1) with Cytochrome C (Cytc) expression, various clinicopathological features, and prognosis in breast cancer (BC) patients. Meanwhile, the correlation of Cytc expression with various clinical features and 5-year disease-free survival (5-DFS) of BC was also investigated. Methods. In vivo, expression of VDAC1 and Cytc was examined in 219 BC tissues and 100 benign breast lesions by immunohistochemical (IHC) analysis. In vitro, MTT and wound healing migration assay were performed to detect the effect of VDAC1 on BC cells. Results. Expression of VDAC1 is conversely associated with Cytc in BC ( P = 0.011 ), especially in triple-negative breast cancer (TNBC) ( P = 0.004 ). Knockdown of VDAC1 inhibited proliferation ( P < 0.001 ) and migration ( P < 0.05 ) of MCF-7 cells. High expression of VDAC1 and low expression of Cytc had a significant association with multiple clinicopathological parameters ( P < 0.05 ) and poor 5-DFS ( P < 0.001 ) in BC. Conclusion. VDAC1 was elevated in BC tissues and conversely associated with Cytc. Detection of VDAC1 may provide guidance for the poor prognosis of BC, especially TNBC.

show abstract

“…The maintenance of cytochrome c inside the mitochondrion is essential for the mitochondrial respiratory function [43]. Once released into the cytosol, cytochrome c binds to apoptotic peptidase activating factor 1 (APAF1), activating the formation of the ring-like apoptosome [44,45]. Apoptosomes activate procaspase 9, which in turn activates the effector caspase 3, resulting in the activation of the apoptotic caspases [46,47].…”

Section: Discussionmentioning

confidence: 99%

Intravitreal Injection of Mitochondrial DNA Induces Cell Damage and Retinal Dysfunction in Rats

Guo

Gan

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Retinal neurodegeneration is induced by a variety of environmental insults and stresses, but the exact mechanisms are unclear. In the present study, we explored the involvement of cytosolic mitochondrial DNA (mtDNA), resulting in the cGAS-STING dependent inflammatory response and apoptosis in retinal damage in vivo.Methods: Retinal injury was induced by white light or intravitreal injection of lipopolysaccharide (LPS). After light- or LPS-induced injury, the amount of cytosolic mtDNA in the retina was detected by PCR. The mtDNA was isolated and used to transfect retinas in vivo. WB and real-time PCR were used to evaluated the activation of cGAS-STING pathway and the levels of apoptosis-associated protein at different times after mtDNA stimulation. Retinal cell apoptosis rate was detected by TUNEL staining. Full-field electroretinography (ERG) was used to assess the retinal function.Results: Light injury and the intravitreal injection of LPS both caused the leakage of mtDNA into the cytoplasm in retinal tissue. After the transfection of mtDNA in vivo, the levels of cGAS, STING, and IFN-β mRNAs and the protein levels of STING, phosph-TBK1, phospho-IRF3, and IFN-β were upregulated. mtDNA stimulation also induced the phosphorylation of caspase 3 and caspase 9. BAX and BAK were increased at both the mRNA and protein levels. The release of cytochrome c from the mitochondria to the cytosol was increased after mtDNA stimulation. The wave amplitudes on ERG decreased and retinal cell apoptosis was detected after mtDNA stimulation.Conclusion: Cytosolic mtDNA triggers an inflammatory response. It also promotes apoptosis and the dysfunction of the retina.

show abstract

Molecular insights on cytochrome c and nucleotide regulation of apoptosome function and its implication in cancer

Cited by 25 publications

References 72 publications

Identification and Functional Analysis of Apoptotic Protease Activating Factor-1 (Apaf-1) from Spodoptera litura

Identification and Functional Analysis of Apoptotic Protease Activating Factor-1 (Apaf-1) from Spodoptera litura

VDAC1 Conversely Correlates with Cytc Expression and Predicts Poor Prognosis in Human Breast Cancer Patients

Intravitreal Injection of Mitochondrial DNA Induces Cell Damage and Retinal Dysfunction in Rats

Contact Info

Product

Resources

About