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Antioxidants & Redox Signaling Jan 2014Autophagy is a highly conserved eukaryotic cellular recycling process. Through the degradation of cytoplasmic organelles, proteins, and macromolecules, and the recycling... (Review)
Review
SIGNIFICANCE
Autophagy is a highly conserved eukaryotic cellular recycling process. Through the degradation of cytoplasmic organelles, proteins, and macromolecules, and the recycling of the breakdown products, autophagy plays important roles in cell survival and maintenance. Accordingly, dysfunction of this process contributes to the pathologies of many human diseases.
RECENT ADVANCES
Extensive research is currently being done to better understand the process of autophagy. In this review, we describe current knowledge of the morphology, molecular mechanism, and regulation of mammalian autophagy.
CRITICAL ISSUES
At the mechanistic and regulatory levels, there are still many unanswered questions and points of confusion that have yet to be resolved.
FUTURE DIRECTIONS
Through further research, a more complete and accurate picture of the molecular mechanism and regulation of autophagy will not only strengthen our understanding of this significant cellular process, but will aid in the development of new treatments for human diseases in which autophagy is not functioning properly.
Topics: Animals; Autophagy; Cell Survival; Humans; Pathology
PubMed: 23725295
DOI: 10.1089/ars.2013.5371 -
International Journal of Molecular... Mar 2023Autophagy is a degradative process to remove damaged or unnecessary cellular components, and it has been implicated in many biological processes during cell survival and...
Autophagy is a degradative process to remove damaged or unnecessary cellular components, and it has been implicated in many biological processes during cell survival and death [...].
Topics: Cell Survival; Autophagy
PubMed: 36902171
DOI: 10.3390/ijms24054744 -
Nature Reviews. Genetics Nov 2020The growth and survival of cells within tissues can be affected by 'cell competition' between different cell clones. This phenomenon was initially recognized between... (Review)
Review
The growth and survival of cells within tissues can be affected by 'cell competition' between different cell clones. This phenomenon was initially recognized between wild-type cells and cells with mutations in ribosomal protein (Rp) genes in Drosophila melanogaster. However, competition also affects D. melanogaster cells with mutations in epithelial polarity genes, and wild-type cells exposed to 'super-competitor' cells with mutation in the Salvador-Warts-Hippo tumour suppressor pathway or expressing elevated levels of Myc. More recently, cell competition and super-competition were recognized in mammalian development, organ homeostasis and cancer. Genetic and cell biological studies have revealed that mechanisms underlying cell competition include the molecular recognition of 'different' cells, signalling imbalances between distinct cell populations and the mechanical consequences of differential growth rates; these mechanisms may also involve innate immune proteins, p53 and changes in translation.
Topics: Animals; Cell Communication; Cell Competition; Cell Survival; Humans; Liver
PubMed: 32778819
DOI: 10.1038/s41576-020-0262-8 -
Current Opinion in Cell Biology Apr 2018The number of mature B cells is carefully controlled by signalling from receptors that support B cell survival. The best studied of these are the B cell antigen receptor... (Review)
Review
The number of mature B cells is carefully controlled by signalling from receptors that support B cell survival. The best studied of these are the B cell antigen receptor (BCR) and BAFFR. Recent work has shown that signalling from these receptors is closely linked, involves the CD19 co-receptor, and leads to activation of canonical and non-canonical NF-κB pathways, ERK1, ERK2 and ERK5 MAP kinases, and PI-3 kinases. Importantly, studies show that investigation of the importance of signalling molecules in cell survival requires the use of inducible gene deletions within mature B cells. This overcomes the limitations of many earlier studies using constitutive gene deletions which were unable to distinguish between requirements for a protein in development versus survival.
Topics: B-Lymphocytes; Cell Survival; Humans; Signal Transduction
PubMed: 29149682
DOI: 10.1016/j.ceb.2017.10.002 -
Medicina 2020
Topics: Apoptosis; Cell Survival; HeLa Cells; Humans
PubMed: 32282324
DOI: No ID Found -
Essays in Biochemistry 2012During cell competition fitter cells take over the tissue at the expense of viable, but less fit, cells, which are eliminated by induction of apoptosis or senescence.... (Review)
Review
During cell competition fitter cells take over the tissue at the expense of viable, but less fit, cells, which are eliminated by induction of apoptosis or senescence. This probably acts as a quality-control mechanism to eliminate suboptimal cells and safeguard organ function. Several experimental conditions have been shown to trigger cell competition, including differential levels in ribosomal activity or in signalling pathway activation between cells, although it is unclear how those differences are sensed and translated into fitness levels. Many of the pathways implicated in cell competition have been previously linked with cancer, and this has led to the hypothesis that cell competition could play a role in tumour formation. Cell competition could be co-opted by cancer cells to kill surrounding normal cells and boost their own tissue colonization. However, in some cases, cell competition could have a tumour suppressor role, as cells harbouring mutations in a subset of tumour suppressor genes are killed by wild-type cells. Originally described in developing epithelia, competitive interactions have also been observed in some stem cell niches, where they play a role in regulating stem cell selection, maintenance and tissue repopulation. Thus competitive interactions could be relevant to the maintenance of tissue fitness and have a protective role against aging.
Topics: Animals; Cell Communication; Cell Death; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Gene Expression Regulation; Genes, Tumor Suppressor; Humans
PubMed: 22928509
DOI: 10.1042/bse0530069 -
Physics in Medicine and Biology Dec 2022Determine the extent of sublethal radiation damage (SRD) in a cell population that received a given dose of radiation and the impact of this damage on cell survival.We...
Determine the extent of sublethal radiation damage (SRD) in a cell population that received a given dose of radiation and the impact of this damage on cell survival.We developed a novel formalism to account for accumulation of SRD with increasing dose. It is based on a very general formula for cell survival that correctly predicts the basic properties of cell survival curves, such as the transition from the linear-quadratic to a linear dependence at high doses. Using this formalism we analyzed extensive experimental data for photons, protons and heavy ions to evaluate model parameters, quantify the extent of SRD and its impact on cell survival.Significant accumulation of SRD begins at doses below 1 Gy. As dose increases, so does the number of damaged cells and the amount of SRD in individual cells. SRD buildup in a cell increases the likelihood of complex irrepairable damage. For this reason, during a dose fraction delivery, each dose increment makes cells more radiosensitive. This gradual radosensitization is evidenced by the increasing slope of survival curves observed experimentally. It continues until the fraction is delivered, unless radiosensitivity reaches its maximum first. The maximum radiosensitivity is achieved when SRD accumulated in most cells is the maximum damage they can repair. After this maximum is reached, the slope of a survival curve, logarithm of survival versus dose, becomes constant, dose independent. The survival curve becomes a straight line, as experimental data at high doses show. These processes are random. They cause large cell-to-cell variability in the extent of damage and radiosensitivity of individual cells.SRD is in effect a radiosensitizer and its accumulation is a significant factor affecting cell survival, especially at high doses. We developed a novel formalism to study this phenomena and reported pertinent data for several particle types.
Topics: Cell Survival; Dose-Response Relationship, Radiation; Radiation Tolerance; Protons; Photons; Relative Biological Effectiveness
PubMed: 36533628
DOI: 10.1088/1361-6560/aca5e7 -
International Journal of Molecular... Jan 2019Malignancy often arises from sophisticated defects in the intricate molecular mechanisms of cells, rendering a complicated molecular ground to effectively target... (Review)
Review
Malignancy often arises from sophisticated defects in the intricate molecular mechanisms of cells, rendering a complicated molecular ground to effectively target cancers. Resistance toward cell death and enhancement of cell survival are the common adaptations in cancer due to its infinite proliferative capacity. Existing cancer treatment strategies that target a single molecular pathway or cancer hallmark fail to fully resolve the problem. Hence, multitargeted anticancer agents that can concurrently target cell death and survival pathways are seen as a promising alternative to treat cancer. Tocotrienols, a minor constituent of the vitamin E family that have previously been reported to induce various cell death mechanisms and target several key survival pathways, could be an effective anticancer agent. This review puts forward the potential application of tocotrienols as an anticancer treatment from a perspective of influencing the life or death decision of cancer cells. The cell death mechanisms elicited by tocotrienols, particularly apoptosis and autophagy, are highlighted. The influences of several cell survival signaling pathways in shaping cancer cell death, particularly NF-κB, PI3K/Akt, MAPK, and Wnt, are also reviewed. This review may stimulate further mechanistic researches and foster clinical applications of tocotrienols via rational drug designs.
Topics: Animals; Apoptosis; Autophagy; Cell Survival; Endoplasmic Reticulum Stress; Humans; Neoplasms; Tocotrienols
PubMed: 30654580
DOI: 10.3390/ijms20020372 -
Biomedicine & Pharmacotherapy =... Sep 2021If mitochondrial energy availability or oxidative metabolism is altered, patients will suffer from insufficient energy supply Phosphocreatine (PCr) not only acts as an... (Review)
Review
If mitochondrial energy availability or oxidative metabolism is altered, patients will suffer from insufficient energy supply Phosphocreatine (PCr) not only acts as an energy carrier, but also acts as an antioxidant and defensive agent to maintain the integrity and stability of the membrane, to maintain ATP homeostasis through regulating mitochondrial respiration. Meanwhile, PCr can enhance calcium balance and reduce morphological pathological changes, ultimately, PCr helps to reduce apoptosis. On the other aspect, the activities of ATP synthase and MitCK play a crucial role in the maintenance of cellular energy metabolic function. It is interesting to note, PCr not only rises the activities of ATP synthase as well as MitCK, but also promotes these two enzymatic reactions. Additionally, PCr can also inhibit mitochondrial permeability transition in a concentration-dependent manner, prevent ROS and CytC from spilling into the cytoplasm, thereby inhibit the release of proapoptotic factors caspase-3 and caspase-9, and eventually, effectively prevent LPS-induced apoptosis of cells. Understandably, PCr prevents the apoptosis caused by abnormal mitochondrial energy metabolism and has a protective role in a non-energy manner. Moreover, recent studies have shown that PCr protects cell survival through PI3K/Akt/eNOS, MAPK pathway, and inhibition of Ang II-induced NF-κB activation. Furthermore, PCr antagonizes oxidative stress through the activation of PI3K/Akt/GSK3b intracellular pathway, PI3K/AKT-PGC1α signaling pathway, while through the promotion of SIRT3 expression to maintain normal cell metabolism. Interestingly, PCr results in delaying the time to enter pathological metabolism through the delayed activation of AMPK pathway, which is different from previous studies, now we propose the hypothesis that the "miRNA-JAK2/STAT3 -CypD pathway" may take part in protecting cells from apoptosis, PCr may be further be involved in the dynamic relationship between CypD and STAT3. Furthermore, we believe that PCr and CypD would be the central link to maintain cell survival and maintain cell stability and mitochondrial repair under the mitochondrial dysfunction caused by oxidative stress. This review provides the modern progress knowledge and views on the molecular mechanism and molecular targets of PCr in a non-energy way.
Topics: Animals; Cell Survival; Energy Metabolism; Humans; Oxidative Stress; Phosphocreatine; Signal Transduction
PubMed: 34174505
DOI: 10.1016/j.biopha.2021.111839 -
Chemistry & Biology Mar 2013Prohibitins (PHBs) are scaffold proteins that modulate many signaling pathways controlling cell survival, metabolism, and inflammation. Several drugs that target PHBs... (Review)
Review
Prohibitins (PHBs) are scaffold proteins that modulate many signaling pathways controlling cell survival, metabolism, and inflammation. Several drugs that target PHBs have been identified and evaluated for various clinical applications. Preclinical and clinical studies indicate that these PHB ligands may be useful in oncology, cardiology, and neurology, as well as against obesity. This review covers the physiological role of PHBs in health and diseases and current developments concerning PHB ligands.
Topics: Animals; Cell Death; Cell Survival; Disease; Drug Discovery; Humans; Ligands; Prohibitins; Repressor Proteins
PubMed: 23521790
DOI: 10.1016/j.chembiol.2013.02.006