Shared developmental roles and transcriptional control of autophagy and apoptosis in <i>Caenorhabditis elegans</i>

Erdélyi, Péter; Borsos, Éva; Takács‐Vellai, Krisztina; Kovács, Tibor; Kovács, Attila; Sigmond, Tímea; Hargitai, Balázs; Pásztor, Líz; SenGupta, Tanima; Dengg, Marlene; Pecsi, Ildiko; Tóth, Judit; Nilsen, Hilde; Vértessy, Beáta G.; Vellai, Tibor

doi:10.1242/jcs.080192

Cited by 37 publications

(28 citation statements)

References 34 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However alone are viable, whereas embryos that are deficient in both autophagy and apoptosis arrest at early developmental stages with severe morphological defects. 75 The studies summarised in this review also suggest that there is a cooperative role of the apoptotic and autophagic pathways in different developmental contexts. It is evident that there is a complex interplay between apoptosis and autophagy, yet the mechanisms remain unknown.…”

Section: Discussionmentioning

confidence: 82%

Cell death by autophagy: facts and apparent artefacts

2011

View full text Add to dashboard Cite

Autophagy (the process of self-digestion by a cell through the action of enzymes originating within the lysosome of the same cell) is a catabolic process that is generally used by the cell as a mechanism for quality control and survival under nutrient stress conditions. As autophagy is often induced under conditions of stress that could also lead to cell death, there has been a propagation of the idea that autophagy can act as a cell death mechanism. Although there is growing evidence of cell death by autophagy, this type of cell death, often called autophagic cell death, remains poorly defined and somewhat controversial. Merely the presence of autophagic markers in a cell undergoing death does not necessarily equate to autophagic cell death. Nevertheless, studies involving genetic manipulation of autophagy in physiological settings provide evidence for a direct role of autophagy in specific scenarios. This article endeavours to summarise these physiological studies where autophagy has a clear role in mediating the death process and discusses the potential significance of cell death by autophagy.

show abstract

Section: Discussionmentioning

confidence: 82%

Cell death by autophagy: facts and apparent artefacts

2011

View full text Add to dashboard Cite

show abstract

“…Similarly, studies in the nematode C. elegans also suggest that autophagy has a pro‐death function. In C. elegans disruption of either the apoptotic or autophagy pathways alone has no profound affect on development, yet the combined disruption to both pathways results in early embryonic lethality 27 . Perturbations in autophagy activity that results in either reduced or increased levels of autophagy are lethal in the nematode.…”

Section: Autophagy In Model Organismsmentioning

confidence: 99%

Autophagy as a pro‐death pathway

2014

View full text Add to dashboard Cite

The evolutionarily conserved catabolic process of autophagy involves the degradation of cytoplasmic components through lysosomal enzymes. Basal levels of autophagy maintain cellular homeostasis and under stress conditions high levels of autophagy are induced. It is often under such stress conditions that high levels of autophagy and cell death have been observed, leading to the idea that autophagy may act as an executioner of cell death. However the notion of autophagy as a cell death mechanism has been controversial and remains mechanistically undefined. There is now growing evidence that in specific contexts autophagy can indeed facilitate cell death. The pro-death role of autophagy is however complicated due to the extensive cross-talk between different signalling pathways. This review summarises the examples of where autophagy acts as a means of cell death and discusses the association of autophagy with the different cell death pathways.

show abstract

“…[8][9][10][11][12][13][14] Hyperactivation of autophagy can also induce massive cell loss. 15,16 A natural, agedependent decline in the autophagic activity can be observed in several organisms and human tissues.…”

Section: Introductionmentioning

confidence: 99%

AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects

Papp¹,

Kovács

Billes

et al. 2016

Autophagy

Self Cite

View full text Add to dashboard Cite

Autophagy is a major molecular mechanism that eliminates cellular damage in eukaryotic organisms. Basal levels of autophagy are required for maintaining cellular homeostasis and functioning. Defects in the autophagic process are implicated in the development of various age-dependent pathologies including cancer and neurodegenerative diseases, as well as in accelerated aging. Genetic activation of autophagy has been shown to retard the accumulation of damaged cytoplasmic constituents, delay the incidence of age-dependent diseases, and extend life span in genetic models. This implies that autophagy serves as a therapeutic target in treating such pathologies. Although several autophagy-inducing chemical agents have been identified, the majority of them operate upstream of the core autophagic process, thereby exerting undesired side effects. Here, we screened a small-molecule library for specific inhibitors of MTMR14, a myotubularin-related phosphatase antagonizing the formation of autophagic membrane structures, and isolated AUTEN-67 (autophagy enhancer-67) that significantly increases autophagic flux in cell lines and in vivo models. AUTEN-67 promotes longevity and protects neurons from undergoing stressinduced cell death. It also restores nesting behavior in a murine model of Alzheimer disease, without apparent side effects. Thus, AUTEN-67 is a potent drug candidate for treating autophagy-related diseases.

show abstract

Shared developmental roles and transcriptional control of autophagy and apoptosis in Caenorhabditis elegans

Cited by 37 publications

References 34 publications

Cell death by autophagy: facts and apparent artefacts

Cell death by autophagy: facts and apparent artefacts

Autophagy as a pro‐death pathway

AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects

Contact Info

Product

Resources

About