Autophagy (or autophagocytosis) (from the Greek auto-, "self" and phagein, "to eat"), is the basic catabolic mechanism that involves cell degradation of unnecessary or dysfunctional cellular components through the actions of lysosomes. The breakdown of cellular components promotes cellular survival during starvation by maintaining cellular energy levels. Autophagy allows the degradation and recycling of cellular components. During this process, targeted cytoplasmic constituents are isolated from the rest of the cell within a double-membraned vesicle known as an autophagosome. The autophagosome then fuses with a lysosome and its cargo is degraded and recycled.
There are three different forms of autophagy that are commonly described; macroautophagy, microautophagy and chaperone-mediated autophagy.
In the context of disease, autophagy has been seen as an adaptive response to stress which promotes survival, whereas in other cases it appears to promote cell death and morbidity.
Hello Tobias,
this paper could be very interesting for you and help you with your question: "The Impact of Autophagy on Cell Death Modalities" by Ryter et al. (2014) published in International Journal of Cell Biology. You can download it here: http://www.hindawi.com/journals/ijcb/2014/502676/
Best regards, Christian
Many thanks, Chris!
International Journal of Cell Biology
Volume 2014 (2014), Article ID 502676, 12 pages
http://dx.doi.org/10.1155/2014/502676
Review Article
The Impact of Autophagy on Cell Death Modalities
Stefan W. Ryter,1,2 Kenji Mizumura,1,2 and Augustine M. K. Choi2
1Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
2Weil Cornell Medical College, 525 East 68th Street, Room M-522, Box 130, New York, NY 10065, USAReceived 11 November 2013; Accepted 18 December 2013; Published 4 February 2014Academic Editor: Claudia GiampietriCopyright © 2014 Stefan W. Ryter et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Autophagy represents a homeostatic cellular mechanism for the turnover of organelles and proteins, through a lysosome-dependent degradation pathway. During starvation, autophagy facilitates cell survival through the recycling of metabolic precursors. Additionally, autophagy can modulate other vital processes such as programmed cell death (e.g., apoptosis), inflammation, and adaptive immune mechanisms and thereby influence disease pathogenesis. Selective pathways can target distinct cargoes (e.g., mitochondria and proteins) for autophagic degradation. At present, the causal relationship between autophagy and various forms of regulated or nonregulated cell death remains unclear. Autophagy can occur in association with necrosis-like cell death triggered by caspase inhibition. Autophagy and apoptosis have been shown to be coincident or antagonistic, depending on experimental context, and share cross-talk between signal transduction elements. Autophagy may modulate the outcome of other regulated forms of cell death such as necroptosis. Recent advances suggest that autophagy can dampen inflammatory responses, including inflammasome-dependent caspase-1 activation and maturation of proinflammatory cytokines. Autophagy may also act as regulator of caspase-1 dependent cell death (pyroptosis). Strategies aimed at modulating autophagy may lead to therapeutic interventions for diseases in which apoptosis or other forms of regulated cell death may play a cardinal role.
Editing a book:
Cell death: apoptosis, autophagy and necrosis!
Period!
Autophagy is mainly survival mechanism specifically under stress conditions
One of the mechanisms of programmed cell death (PCD) is associated with the appearance of autophagosomes and depends on autophagy proteins. This form of cell death most likely corresponds to a process that has been morphologically defined as autophagic PCD. One question that constantly arises, however, is whether autophagic activity in dying cells is the cause of death or is actually an attempt to prevent it. Morphological and histochemical studies so far did not prove a causative relationship between the autophagic process and cell death. In fact, there have recently been strong arguments that autophagic activity in dying cells might actually be a survival mechanism. Studies of the metamorphosis of insects have shown cells undergoing a form of PCD that appears distinct from other forms; these have been proposed as examples of autophagic cell death.[39] Recent pharmacological and biochemical studies have proposed that survival and lethal autophagy can be distinguished by the type and degree of regulatory signaling during stress particularly after viral infection.[40] Although promising, these findings have not been examined in non-viral systems.
An article frequently cited is this one
Review
Cell Death and Differentiation (2005) 12, 1528–1534. doi:10.1038/sj.cdd.4401777
Another way to die: autophagic programmed cell death
Edited by G Melino
Y Tsujimoto1,2 and S Shimizu1,2
1Laboratory of Molecular Genetics, Department of Medical Genetics, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
2SORST of Japan Science Technology Corp., 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Correspondence: Y Tsujimoto, Laboratory of Molecular Genetics, Department of Medical Genetics, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871 Japan. Tel: +81-6-6879-3360; Fax: +81-6-6879-3369; E-mail: [email protected]
Received 6 May 2005; Revised 18 August 2005; Accepted 18 August 2005.
Top of page
Abstract
Programmed cell death (PCD) is one of the important terminal paths for the cells of metazoans, and is involved in a variety of biological events that include morphogenesis, maintenance of tissue homeostasis, and elimination of harmful cells. Dysfunction of PCD leads to various diseases in humans, including cancer and several degenerative diseases. Apoptosis is not the only form of PCD. Recent studies have provided evidence that there is another mechanism of PCD, which is associated with the appearance of autophagosomes and depends on autophagy proteins. This form of cell death most likely corresponds to a process that has been morphologically defined as autophagic PCD. The present review summarizes recent experimental evidence about autophagic PCD and discusses some aspects of this form of cell death, including the mechanisms that may distinguish autophagic death from the process of autophagy involved in cell survival.
But the most recent review I read is the following one
International Journal of Cell Biology
Volume 2014 (2014), Article ID 502676, 12 pages
http://dx.doi.org/10.1155/2014/502676
Review Article
The Impact of Autophagy on Cell Death Modalities
Stefan W. Ryter,1,2 Kenji Mizumura,1,2 and Augustine M. K. Choi2
1Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
2Weil Cornell Medical College, 525 East 68th Street, Room M-522, Box 130, New York, NY 10065, USA
Received 11 November 2013; Accepted 18 December 2013; Published 4 February 2014
Academic Editor: Claudia Giampietri
Copyright © 2014 Stefan W. Ryter et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Autophagy represents a homeostatic cellular mechanism for the turnover of organelles and proteins, through a lysosome-dependent degradation pathway. During starvation, autophagy facilitates cell survival through the recycling of metabolic precursors. Additionally, autophagy can modulate other vital processes such as programmed cell death (e.g., apoptosis), inflammation, and adaptive immune mechanisms and thereby influence disease pathogenesis. Selective pathways can target distinct cargoes (e.g., mitochondria and proteins) for autophagic degradation. At present, the causal relationship between autophagy and various forms of regulated or nonregulated cell death remains unclear. Autophagy can occur in association with necrosis-like cell death triggered by caspase inhibition. Autophagy and apoptosis have been shown to be coincident or antagonistic, depending on experimental context, and share cross-talk between signal transduction elements. Autophagy may modulate the outcome of other regulated forms of cell death such as necroptosis. Recent advances suggest that autophagy can dampen inflammatory responses, including inflammasome-dependent caspase-1 activation and maturation of proinflammatory cytokines. Autophagy may also act as regulator of caspase-1 dependent cell death (pyroptosis). Strategies aimed at modulating autophagy may lead to therapeutic interventions for diseases in which apoptosis or other forms of regulated cell death may play a cardinal role.
Autophagy first described by Christian De Duve in 1963 is the basic catabolic mechanism that involves cell degradation of unnecessary or duysfunctional components though the action of lysosomes. In the context of disease, autophagy has been seen as an adaptative response to stress which promotes survival, whereas in other cases it promotes cell death and morbidity.
I agree with Nabil Eid Autophagy is mainly survival mechanism specifically under stress conditions. There are diverse forms of autophagy.
I recommend you to read reviews original articles of leaders in the field Anna-Maria Cuervos and Guido Kroemer
Nat Cell Biol. 2015 Feb 16. doi: 10.1038/ncb3101. [Epub ahead of print]
Huntingtin functions as a scaffold for selective macroautophagy.
Rui YN1, Xu Z1, Patel B2, Chen Z1, Chen D1, Tito A3, David G4, Sun Y1, Stimming EF5, Bellen HJ6, Cuervo AM7, Zhang S8.
Author information
Abstract
Selective macroautophagy is an important protective mechanism against diverse cellular stresses. In contrast to the well-characterized starvation-induced autophagy, the regulation of selective autophagy is largely unknown. Here, we demonstrate that Huntingtin, the Huntington disease gene product, functions as a scaffold protein for selective macroautophagy but it is dispensable for non-selective macroautophagy. In Drosophila, Huntingtin genetically interacts with autophagy pathway components. In mammalian cells, Huntingtin physically interacts with the autophagy cargo receptor p62 to facilitate its association with the integral autophagosome component LC3 and with Lys-63-linked ubiquitin-modified substrates. Maximal activation of selective autophagy during stress is attained by the ability of Huntingtin to bind ULK1, a kinase that initiates autophagy, which releases ULK1 from negative regulation by mTOR. Our data uncover an important physiological function of Huntingtin and provide a missing link in the activation of selective macroautophagy in metazoans.
There is a recent special issue
Cell Death Differ. 2015 Mar;22(3):365-6. doi: 10.1038/cdd.2014.236.
Autophagy in stress and disease.
Maiuri MC, Kroemer G.
Cell Death and Differentiation (2015) 22, 365–366; doi:10.1038/cdd.2014.236
Autophagy in stress and disease
M Chiara Maiuri and G Kroemer
Macroautophagy, here referred to as ‘autophagy,’ constitutes one of the most spectacular phenomena in cell biology beyond cell fusion, cell division, differentiation and demise. Metaphorically spoken, it constitutes a process in which the cell sequesters portions of itself in its stomach (the autophagosomes) and then assures their complete degradation in its digestive tract (the lysosomes).
Autophagy constitutes one of the most elementary reactions that a cell may have to adapt itself to a changing microenvironment. For instance, in conditions of dwindling external resources, be it nutrients, growth factors or oxygen, the cell may mobilize its stock of potentially energy-rich macromolecules by autophagy, thereby converting proteins and lipids into life-preserving fuel for bioenergetic reactions. In addition, the cell can take advantage of the autophagic machinery to remove damaged, dysfunctional and potentially harmful organelles such as uncoupled mitochondria from its cytoplasm or to destroy useless and even dangerous protein aggregates. Hence, autophagy constitutes an essential mechanism for the recycling of cytoplasmic material and in fine cleaning and rejuvenating extranuclear compartments, especially in non-dividing cells such as neurons or cardiomyocytes. Beyond its homeostatic function, autophagy also has a major role in hormetic reactions. Hormesis can be defined as a process in which the exposure of cells, organs or organisms to a mild stress allows them to mount an adaptive response that allow them to tolerate a later, stronger and normally lethal stress. One well-known example of hormesis is ischemic preconditioning in which a short episode of ischemia reduces the death of heart muscle cells to an otherwise fatal infarction. In this context, autophagy induction has a major role in increasing the robustness of the system, protecting it from deadly stress. Nonetheless, there are also specific situations in which an excess of autophagy may ultimately cause the death of cells by excessive self-digestion. This potentially lethal role of autophagy has received the name of ‘autosis’.
The present Special Issue of Cell Death & Differentiation deals with the physiological and pathological functions of autophagy in cell stress and disease. Liu and Levine1 provide an overview over the potential roles of autosis and autophagic cell death in health and disease. Filomeni et al.2 demonstrate the importance of autophagy regulation by reactive oxygen species and reactive nitrogen species in the context of cytoplasmic processes and DNA damage signaling. Orhon et al.3 insist on the important role of primary cilia, which are microtubule-based structures located at the cell surface of many cell types, as potential sensors of autophagy-inducing stimuli that are in turn affected in their biogenesis and function by autophagic responses. Nikoletopoulou et al.4 demonstrate the essential role of autophagy for the normal function of neurons in model organisms such as Caenorhabditis elegans, as well as the potential role of autophagy in the the unwarranted demise of neurons induced by pathological stimuli including overexcitation.
Cell Death Differ. 2015 Mar;22(3):389-397. doi: 10.1038/cdd.2014.171. Epub 2014 Oct 31.
Autophagy and regulation of cilia function and assembly.
Orhon I, Dupont N, Pampliega O, Cuervo AM, Codogno P.
Author information
Abstract
Motile and primary cilia (PC) are microtubule-based structures located at the cell surface of many cell types. Cilia govern cellular functions ranging from motility to integration of mechanical and chemical signaling from the environment. Recent studies highlight the interplay between cilia and autophagy, a conserved cellular process responsible for intracellular degradation. Signaling from the PC recruits the autophagic machinery to trigger autophagosome formation. Conversely, autophagy regulates ciliogenesis by controlling the levels of ciliary proteins. The cross talk between autophagy and ciliated structures is a novel aspect of cell biology with major implications in development, physiology and human pathologies related to defects in cilium function.
Degradation of self for purpose of recycling...either as normal function or if cell starve energetically they shall eat tehmselves...Some people have called for a cell death by autophagy as they wish, but I think it is wrong, a cell cannot eat itself to make itself die, but maybe as a result of it or its starvation, or cytotoxicity as a cause of death.
Tobias,
Autophagy can act in both a pro-survival and a pro-death fashion, depending on the type and duration of the stressor. There are several excellent reviews on the subject that outline the conditions in which autophagy leads to cell death independent of apoptosis or necrosis. Many believe that all three cell death mechanisms exist on a type of continuum whereby each can elicit death alone, or in concern or upstream of another form of cell death. Hope this helps!
A perspective on autophagy in cancer:
Autophagy is a process that describes the degradation and recycling of proteins and intracellular components in response to nutrient starvation or other stresses.
At the early stage of tumor development, autophagy functions as a tumor suppressor. Expression of beclin 1, a mammalian orthologue of the yeast autophagy-related gene Atg6, reduces tumorigenic capacity through induction of autophagy. Mice that are Beclin 1+/- display a remarkable increase in the incidence of lung cancer, hepatocellular carcinoma and lymphoma.
At advanced stages of tumor development, autophagy promotes tumor progression. The tumor cells that are located in the central area of the tumor mass undergo autophagy to survive low-oxygen and low-nutrient conditions.
Autophagy protects some cancer cells against therapeutic stress (e.g., chemotherapy) by blocking the apoptotic pathway ('protective autophagy'). By contrast, other cancer cells undergo autophagic cell death after cancer therapies.
Autophagy is induced mainly through the phosphatidylinositol 3-phosphate kinase (PI3K)–AKT–mTOR (mammalian target of rapamycin) signalling pathway. Other pathways are also involved.
Manipulation of autophagy has the potential to improve anticancer therapeutics. When tumor cells induce protective autophagy, inhibition of autophagy could sensitize tumor cells to the treatment by activating apoptosis. On the other hand, induction of autophagic cell death can also have a therapeutic value.
Hippert M M et al. Cancer Res 2006;66:9349-9351
Chen Y , Klionsky D J J Cell Sci 2011;124:161-170
Amaravadi R K et al. Clin Cancer Res 2011;17:654-666
Congratulqtions for the explanations of Tobias Ntuli. We also have discussed this point in our Ultratsructural Pathology publications in 2010, 2014 about autoschizis as a new mode of cell death for tumor cells, found in vitro and in vivo (in xenotransplants).
Dear Tobias,
I think that you can find very interesting responses in the attached articles, which are the "World consensus" (...) in these fields of cell death pathways...
However, difficult to read them "easily" or "rapidly" ...
More "funny" articles (also here attached) about "cell death" relate to ... cell "canibalism" ... (from more than top scientists!!).
Best regards
Robert
Dear Professor Kiss:
Many thanks!
Best regards,
Doctor Tobias M. Ntuli
FYKI: in thread: https://www.researchgate.net/post/What_is_the_difference_between_Autophagy_and_Phagocytosis
one can find the last answer (011, 4 days ago = 20th of May 2019) ) by @ Chenghe FAN
who points to an article (REVIEW) by Oczypok et al, 2013
in American Journal of Pathology 182(3)
DOI: 10.1016/j.ajpath.2012.12.017
" It's a Cell-Eat-Cell World: Autophagy and Phagocytosis. "
(cf. ResearchGate:
Article It's a Cell-Eat-Cell World: Autophagy and Phagocytosis.
This colleague also pointed to: www.genemedi.net/i/autophagy .
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