Apoptosome-deficient Cells Lose Cytochrome<i>c</i>through Proteasomal Degradation but Survive by Autophagy-dependent Glycolysis

Ferraro, Elisabetta; Pulicati, Angela; Cencioni, Maria Teresa; Cozzolino, Mauro; Navoni, Francesca; Martino, Simona Di; Nardacci, Roberta; Carrı̀, Maria Teresa; Cecconi, Francesco

doi:10.1091/mbc.e07-09-0858

Cited by 47 publications

(44 citation statements)

References 50 publications

(68 reference statements)

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“…However, in order to assess the PONR, a combination of recommended detection methods 1,5,10,14 is suggested. Further it which control characteristic 39 and often progressively developing 40 morphological changes. Control of the PONR position through the cell's metabolic efforts would ensure the highest likelihood of cellular preservation.…”

Section: Dynamics Within Modes Of Cell Deathmentioning

confidence: 97%

“…The cell protects itself from dying, therefore is suggested that kinetic parameters for autophagy, apoptosis and necrosis as well as cell specific parameters, intra-and extracellular metabolic parameters and insult parameters be carefully considered (Table 1). For example, a combination of data on basal autophagic flux, 10,23,41 the time needed to reach its maximal attainable activity, as well as vital dye uptake dynamics [42][43][44] and onset of dissipation of mitochondrial transmembrane potential ∆Ψ m 33 should be placed into context with the cell's metabolic substrate preference and ATP household over time 39 in order to describe the PONR. It is crucial that multiple parameters be acquired at multiple points in time, and examined in context with one another, to capture the dynamic character of temporal signalling during cellular response.…”

Section: Autophagy and The Dynamics Between Modes Of Cell Deathmentioning

confidence: 99%

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Cell death: A dynamic response concept

Loos

Engelbrecht²

2009

Autophagy

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Autophagy, apoptosis and necrosis have previously been described as distinct static processes that induce and execute cell death. Due to an increased use of novel techniques in mapping cellular death-techniques which allow for reporting of real-time data-the existence of "grey zones" between cell death modes and the existence of the "point of no return" within these have been revealed. This revelation demands the integration of new concepts in describing the cellular death process. Furthermore, since the contribution of autophagy in cell death or cell survival is still poorly understood, it is important to accurately describe its function within the dynamic framework of cell death.In this review cell death is viewed as a dynamic and integrative cellular response to ensure the highest likelihood of self-preservation. Suggestions are offered for conceptualizing cell death modes and their morphological features, both individually and in relation to one another. It addresses the need for distinguishing between dying cells and dead cells so as to better locate and control the onset of cell death. Most importantly, the fundamental role of autophagy, autophagic flux, and the effects of the intracellular metabolic environment on the kinetics of the cell death modes are stressed. It also contextualizes the kinetic dimension of cell death as a process and aims to contribute towards a better understanding of autophagy as a key mechanism within this process. Understanding the dynamic nature of the cell death process and autophagy's central role can reveal new insight for therapeutic intervention in preventing cell death.

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Section: Dynamics Within Modes Of Cell Deathmentioning

confidence: 97%

Section: Autophagy and The Dynamics Between Modes Of Cell Deathmentioning

confidence: 99%

Cell death: A dynamic response concept

Loos

Engelbrecht²

2009

Autophagy

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“…48 By targeting glycogen, lipids and proteins to lysosomes, autophagy guides the breakdown of these macromolecules, thereby producing metabolic precursors that can sustain oxidative phosphorylation and glycolysis. 49,50 In cancer cells from solid undernourished tumors, response to radiotherapy or DNA-damaging chemotherapy triggers ATP production by autophagy, which may have an essential role in DNA repair ( Figure 1, box ii). Supporting this hypothesis, the inhibition of autophagy suppressed ATP generation and increased mitotic catastrophe in glioma cells treated with temozolomide (TMZ).…”

Section: The Role Of Autophagy In Dna Repairmentioning

confidence: 99%

Autophagy and genomic integrity

et al. 2013

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DNA lesions, constantly produced by endogenous and exogenous sources, activate the DNA damage response (DDR), which involves detection, signaling and repair of the damage. Autophagy, a lysosome-dependent degradation pathway that is activated by stressful situations such as starvation and oxidative stress, regulates cell fate after DNA damage and also has a pivotal role in the maintenance of nuclear and mitochondrial genomic integrity. Here, we review important evidence regarding the role played by autophagy in preventing genomic instability and tumorigenesis, as well as in micronuclei degradation. Several pathways governing autophagy activation after DNA injury and the influence of autophagy upon the processing of genomic lesions are also discussed herein. In this line, the mechanisms by which several proteins participate in both DDR and autophagy, and the importance of this crosstalk in cancer and neurodegeneration will be presented in an integrated fashion. At last, we present a hypothetical model of the role played by autophagy in dictating cell fate after genotoxic stress.

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“…Some studies conclude that autophagy could be a protective procedure for cells and tissues to sustain hypoxia/ ischemia. 26,27) On the other hand, there are also a number of papers documenting a deleterious role for autophagy. 17,28) A reliable explanation for these phenomena is that autophagy is primarily a protective process to maintain homeostasis under the stress of cerebral ischemia/reperfusion.…”

Section: )mentioning

confidence: 99%

Intranasal Ginsenoside Rb1 Targets the Brain and Ameliorates Cerebral Ischemia/Reperfusion Injury in Rats

Jiang

Zhou

et al. 2011

Biological & Pharmaceutical Bulletin

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Panax ginseng is a highly valued medicinal herb in Eastern society. It has also been well accepted in the West over the past decades. Ginsenosides, a major group of phytoestrogens, are the main active components of ginseng. Ginsenoside Rb1 (GRb1) is one of the most abundant ginsenosides in ginseng extract, accounting for 27-42% of the total ginsenosides. 1) It has been proven to alleviate many central nervous system (CNS) disorders, including ischemic stroke. The mechanisms of GRb1 in ameliorating cerebral ischemia/reperfusion involve anti-oxidation, 2) up-regulating neurotrophic factors, 3) anti-apoptosis 3,4) and neurogenesis induction. 5)However, recent data on the pharmacokinetics of Rb1 show that its absolute oral bioavailability is as low as 4.35% in rats. Low membrane permeability dominates the extent of absorption.6,7) Also, some studies have demonstrated that the effects of 0.1-100 nmol/kg intracerebroventricular GRb1 on ischemic injury are comparable to that of several mg/kg GRb1 systemically administrated. 3,4,8) These results suggest that GRb1 might have difficulty entering the CNS. The blood-brain barrier (BBB) or other specialized CNS barriers are the main obstacles to the delivery of many potentially therapeutic and diagnostic compounds to specific areas of the brain. Large (Ͼ500 Da) hydrophilic molecules such as peptides and proteins are generally excluded, unless they can be transferred by specific receptor-mediated transcytosis or by the less specific adsorptive-mediated transcytosis.9,10) With a relatively large molecular weight of 1109.46 and an amphiphilic molecular structure, Rb1 is predicted too hard to penetrate the BBB.In recent years, intranasal delivery has gained a significant amount of attention as a convenient and reliable noninvasive method for the systemic administration of drugs. Moreover, it has been proven to rapidly target therapeutics to the CNS, bypassing the BBB, which is particularly suitable for CNS drugs with a large molecular weight and systemic side effects.11) Intranasal Ginsenoside Rg3 has been shown to have anti-fatigue effects.12) The distribution of Panax notoginseng saponins (containing GRb1) in the form of its suspension in plasma after intranasal administration has been tested. 13)However, the distribution of ginsenosides in the brain after intranasal or any other delivery method is still unknown.Macroautophagy (autophagy) is an evolutionarily conserved mechanism for the degradation of cellular proteins and organisms. The process of autophagy is the assembly and transformation of double-membrane vesicles.14) In the last decade, it has been recognized to play a critical role in removing protein aggregates, as well as damaged or excess organelles, to maintain intracellular homeostasis and keep the cell healthy. However, excessive or inappropriate autophagy can also lead to cell death (autophagy related cell death). 15)In the brain, autophagy occurs at a low level under physiological conditions. However, this pathway is rapidly up-regulated under environmental str...

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Apoptosome-deficient Cells Lose Cytochromecthrough Proteasomal Degradation but Survive by Autophagy-dependent Glycolysis

Cited by 47 publications

References 50 publications

Cell death: A dynamic response concept

Cell death: A dynamic response concept

Autophagy and genomic integrity

Intranasal Ginsenoside Rb1 Targets the Brain and Ameliorates Cerebral Ischemia/Reperfusion Injury in Rats

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