I think autophagy controls the death of my cells: What do I do to get my paper published?

Many people are studying how autophagy intersects with cell death. While most of those studies relate to autophagy acting as a protective mechanism (e.g., to block apoptosis), many papers conclude that autophagy is a death mechanism, and there is a widespread belief that autophagy (in most, but not all cases, we are talking about macroautophagy) can both kill and protect cells depending on the circumstances. Not surprisingly therefore, many of the papers submitted to Autophagy study the relationship between autophagy and cell death.     

Protocols,Toolboxes and Resource papers

In the August 2009 issue of Autophagy, I indicated that we were launching a new category of article, Protocols. At that time, I noted that we would ultimately be placing these articles on a new site online. Well, that time has finally arrived (see www.landesbioscience.com/journals/autophagy/protocols/ for links to these papers). Therefore, it seems appropriate for me to briefly distinguish among three types of community-oriented papers, Protocol, Toolbox and Resource.     

Autophagy in Dictyostelium: Mechanisms,regulation and disease in a simple biomedical model

Autophagy is a fast-moving field with an enormous impact on human health and disease. Understanding the complexity of the mechanism and regulation of this process often benefits from the use of simple experimental models such as the social amoeba Dictyostelium discoideum. Since the publication of the first review describing the potential of D. discoideum in autophagy, significant advances have been made that demonstrate both the experimental advantages and interest in using this model. Since our previous review, research in D. discoideum has shed light on the mechanisms that regulate autophagosome formation and contributed significantly to the study of autophagy-related pathologies. Here, we review these advances, as well as the current techniques to monitor autophagy in D. discoideum. The comprehensive bioinformatics search of autophagic proteins that was a substantial part of the previous review has not been revisited here except for those aspects that challenged previous predictions such as the composition of the Atg1 complex. In recent years our understanding of, and ability to investigate, autophagy in D. discoideum has evolved significantly and will surely enable and accelerate future research using this model.     

Autophagy in food biotechnology

The purpose of this review is not to explain autophagy (as clearly there are a plethora of reviews and research papers on the topic) but to provide the autophagy-savvy reader with an overview of the impact of autophagy research on a number of current topics in food biotechnology. To understand this connection, we need to remember that autophagy is, at the end of the day, a type of stress response. Since as humans we are heterotrophic eukaryotic organisms, our cells, and the cells of those organisms that we consume, use autophagy as part of the day-to-day business of living. Thus, a number of food biotechnology processes such as brewing and winemaking employ eukaryotic organisms under autophagy-inducing conditions, as noted below. In addition, food spoilage processes also involve eukayotic organisms and these processes also involve physiological aspects that impinge on autophagy. Finally, the recently introduced concept of “functional foods” introduces the possibility of engineering foodstuff for the induction or inhibition of autophagy in the consumer, with a potential promise of health benefits that merits further research.

In this review, we will provide a perspective on the current literature in these three areas, their relationship to current basic research in autophagy, and their future applicative potential.     

List of biography and history published mostly in <Emphasis Type="Italic">Photosynthesis Research</Emphasis>, 1988–2008

As an outgoing Editor of the Historical Corner of Photosynthesis Research, I present here the following list of papers of historical interest for the benefit of all. The first paper I published was: Govindjee (1988) The Discovery of Chlorophyll–protein Complex by Emil L. Smith during 1937–1941. Photosynth Res 16:285–289. In order to bring to the readers this List of references on the historical papers published in this journal (and some even elsewhere), I have organized these papers under the following headings (some are arbitrarily assigned to a particular section since they may fit in more than one section): (I) biographies (that include obituaries and tributes, arranged alphabetically, with dates of birth and death); (II) recognitions of scientists (arranged alphabetically) by others; (III) personal perspectives (arranged alphabetically); (IV) historical papers (first chronologically, by the year of publication, and then alphabetically by the names of the editors); (V) special issues of Photosynthesis Research (chronologically by the year of publication and then alphabetically by the names of editors); and lastly (VI) Conferences (available reports in Photosynthesis Research). I will appreciate readers to send me (by e-mail: gov@illinois.edu) corrections, if any, and additional references from other journals. “The firefly seems afire, the sky looks flat; Yet sky and fly are neither this nor that”     

Species Distribution Models and Impact Factor Growth in Environmental Journals: Methodological Fashion or the Attraction of Global Change Science

In this work, I evaluate the impact of species distribution models (SDMs) on the current status of environmental and ecological journals by asking the question to which degree development of SDMs in the literature is related to recent changes in the impact factors of ecological journals. The hypothesis evaluated states that research fronts are likely to attract research attention and potentially drive citation patterns, with journals concentrating papers related to the research front receiving more attention and benefiting from faster increases in their impact on the ecological literature. My results indicate a positive relationship between the number of SDM related articles published in a journal and its impact factor (IF) growth during the period 2000–09. However, the percentage of SDM related papers in a journal was strongly and positively associated with the percentage of papers on climate change and statistical issues. The results support the hypothesis that global change science has been critical in the development of SDMs and that interest in climate change research in particular, rather than the usage of SDM per se, appears as an important factor behind journal IF increases in ecology and environmental sciences. Finally, our results on SDM application in global change science support the view that scientific interest rather than methodological fashion appears to be the major driver of research attraction in the scientific literature.     

Immunoamphisomes in dendritic cells amplify TLR signaling and enhance exogenous antigen presentation on MHC-II

Autophagy, a specialized lysosomal degradation pathway, has proven to be a potent cell-autonomous defense mechanism against a range of intracellular microbes. In addition, autophagy emerged recently as a critical regulator of innate and adaptive immune responses. Links between autophagy and innate immunity are being progressively unveiled. For instance, several TLR (Toll-Like Receptor) agonists upregulate autophagy flux in immune cell types such as DC (dendritic cells) or macrophages. Conversely, and perhaps surprisingly, is the observation that TLR7-mediated responses might depend on autophagy in plasmacytoid DC, thus suggesting a more complex link between TLR-dependent responses and autophagy. Recently, the demonstration that NOD2 increases autophagy suggests that innate immune responses initiated via a broad range of pathogen recognition receptors can regulate autophagy. In addition to its involvement in innate immune responses, autophagy regulates adaptive immune responses via both MHC class I and class II molecules depending on the cellular context and the nature of the antigen.     

Reviewing Literature in Bioethics Research: Increasing Rigour in Non‐Systematic Reviews

The recent interest in systematic review methods in bioethics has highlighted the need for greater transparency in all literature review processes undertaken in bioethics projects. In this article, I articulate features of a good bioethics literature review that does not aim to be systematic, but rather to capture and analyse the key ideas relevant to a research question. I call this a critical interpretive literature review. I begin by sketching and comparing three different types of literature review conducted in bioethics scholarship. Then, drawing on Dixon‐Wood's concept of critical interpretive synthesis, I put forward six features of a good critical interpretive literature review in bioethics: answering a research question, capturing the key ideas relevant to the research question, analysing the literature as a whole, generating theory, not excluding papers based on rigid quality assessment criteria, and reporting the search strategy.     

The role of cell signalling in the crosstalk between autophagy and apoptosis

Not surprisingly, the death of a cell is a complex and well controlled process. For several decades, apoptosis, the first genetically programmed death process to be identified has taken centre stage as the principal mechanism of programmed cell death (type I cell death) in mammalian tissues. Apoptosis has been extensively studied and its contribution to the pathogenesis of disease well documented. However, apoptosis does not function alone in determining the fate of a cell. More recently, autophagy, a process in which de novo formed membrane enclosed vesicles engulf and consume cellular components, has been shown to engage in complex interplay with apoptosis. As a result, cell death has been subdivided into the categories apoptosis (Type I), autophagic cell death (Type II), and necrosis (Type III). The boundary between Type I and II cell death is not completely clear and as we will discuss in this review and perhaps a discrete difference does not exist, due to intrinsic factors among different cell types and crosstalk among organelles within each cell type. Apoptosis may begin with autophagy and autophagy can often end with apoptosis, inhibition or a blockade of caspase activity may lead a cell to default into Type II cell death from Type I.     

A human autophagy interaction network

The original “Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes” has been well received and used by many researchers and authors. I consider these to be very important guidelines that require a consensus among the researchers in the field, because they are used by authors to defend against inappropriate reviewers’ comments, and by reviewers to point out to editors the flaws in research papers. Accordingly, I decided it was time to revise and update the guidelines. After all, the field has expanded substantially, as has the range of model systems being used to analyze autophagy. As a result, the list of authors has similarly increased. In addition, this version of the guidelines is not limited to higher eukaryotes nor to macroautophagy. Here, I explain the approach used to invite authors to participate in the revised guidelines, and briefly demonstrate one aspect of their utility.     

自噬的检测方法及评述

细胞自噬是广泛存在于真核细胞内的一种降解途径,在机体发育过程中、在生理和病理状况下都起重要作用。近年,自噬成为热点研究领域,但少有论文深入分析不同检测方法得来的数据在研究中的不同意义,说明不同检测方法所获的结果的优缺点和适用条件。本文拟对哺乳动物细胞自噬检测方法进行归类、介绍及评述,旨在为研究工作中自噬检测方法的选择和研究结果的解释起帮助作用。     

A human autophagy interaction network

The original "Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes" has been well received and used by many researchers and authors. I consider these to be very important guidelines that require a consensus among the researchers in the field, because they are used by authors to defend against inappropriate reviewers' comments, and by reviewers to point out to editors the flaws in research papers. Accordingly, I decided it was time to revise and update the guidelines. After all, the field has expanded substantially, as has the range of model systems being used to analyze autophagy. As a result, the list of authors has similarly increased. In addition, this version of the guidelines is not limited to higher eukaryotes nor to macroautophagy. Here, I explain the approach used to invite authors to participate in the revised guidelines, and briefly demonstrate one aspect of their utility.     

Dissecting the localization and function of Atg18, Atg21 and Ygr223c

Atg18p and Atg21p are two highly homologous yeast autophagy proteins. Atg18p functions in both autophagy and the selective Cvt-pathway, while the function of Atg21p is restricted to the Cvt-pathway. The yeast genome encodes with Ygr223cp (Hsv2p) a third member of this protein family. So far no function has been assigned to Ygr223cp. By colocalization with the endosomal marker Snf7-RFP and an RFP-tagged FYVE domain, we here identify the localization of a pool of Atg18p, Atg21p and Ygr223cp at endosomes. Endosomal recruitment of all three proteins depends on PtdIns3P generated by the Vps34-complex II containing Vps38p, but not on the function of the Vps34-complex I. Since only the Vps34-complex I is essential for autophagy, we expect that at endosomes Atg18p, Atg21p and Ygr223cp have a function distinct from autophagy. Some Vps Class D mutants involved in Golgi-to-endosome transport are required for the endosomal recruitment of GFP-Atg18p, -Atg21p and –Ygr223cp. These include the Qa-SNARE Pep12p, its SM protein Vps45p, the Rab GTPase Vps21p and the Rab effector Vac1p. Deletion of ATG18, ATG21 and YGR223c, alone or simultaneously has no obvious function on the MVB-pathway and CPY-sorting. However, overexpression of ATG21 leads to CPY secretion. We further show, to our knowledge for the first time that Ygr223cp affects an autophagic process, namely micronucleophagy.     

Celebrating 20 years of historical papers in Photosynthesis Research

This Editorial has four goals: (1) to inform the readers of ‘Photosynthesis Research‘ about the past of the ‘Historical corner’; which began 20 years ago; (2) to encourage photosynthesis researchers and historians of science to contact me for publishing papers of historical interest; these include: (a) Obituaries and Tributes; (b) historical papers on current and past discoveries and controversies; (c) history of research in specific laboratories, or in specific countries, or at specific conferences; (d) Personal perspectives (not discussed any further); (3) to encourage researchers not to discard, but to save correspondence and data of their discoveries for the future historians by donating them to their Archives, when appropriate (not discussed any further); and (4) to reinforce to the readers that the concept of two-light reaction and two-pigment system was already there in 1959. I mention here three key papers presented at the IX^th International Botanical Congress, held at Montreal Canada (in August, 1959) prior to the famous April 9, 1960 paper by Robert Hill and Fay Bendall on the ‘Z-scheme’ of photosynthesis, that was based on thermodynamic and energetic considerations. ^★ This Historical corner Editorial is dedicated to Bessel Kok (1918–1978).     

Autophagy and cancer therapy

Autophagy is a dynamic process of protein degradation, which is typically observed during nutrient deprivation. Recently, interest in autophagy has been renewed among oncologists, because different types of cancer cells undergo autophagy after various anticancer therapies. This type of nonapoptotic cell death has been documented mainly by observing morphological changes, e.g., numerous autophagic vacuoles in the cytoplasm of dying cells. Thus, autophagic cell death is considered programmed cell death type II, whereas apoptosis is programmed cell death type I. These two types of cell death are predominantly distinctive, but many studies demonstrate cross-talk between them. Whether autophagy in cancer cells causes death or protects cells is controversial. In multiple studies, autophagy has been inhibited pharmacologically or genetically, resulting in contrasting outcomes--survival or death--depending on the specific context. Interestingly, the regulatory pathways of autophagy share several molecules with the oncogenic pathways activated by tyrosine kinase receptors. Tumor suppressors such as Beclin 1, PTEN and p53 also play an important role in autophagy induction. Taken together, these accumulating data may lead to development of new cancer therapies that manipulate autophagy.     

Autophagy: in sickness and in health

The degradation of intracellular components in lysosomes (autophagy) has recaptured the attention of cell biologists in recent years. The main reason for this renewed interest is the dissection of the molecular machinery that participates in this process, because the identification of new intracellular elements involved in autophagy has provided new tools to trace, quantify and manipulate autophagy in a growing number of organisms. As a result, a better understanding of the physiological roles of autophagy, the consequences of its malfunctioning and its participation in different pathological processes has emerged. This article reviews our current knowledge of the role of autophagy in disease and the efforts to reconcile its proposed dual function as both a cell protector and a cell killer.     

Discovery of pan autophagy inhibitors through a high-throughput screen highlights macroautophagy as an evolutionarily conserved process across 3 eukaryotic kingdoms

Due to the involvement of macroautophagy/autophagy in different pathophysiological conditions such as infections, neurodegeneration and cancer, identification of novel small molecules that modulate the process is of current research and clinical interest. In this work, we developed a luciferase-based sensitive and robust kinetic high-throughput screen (HTS) of small molecules that modulate autophagic degradation of peroxisomes in the budding yeast Saccharomyces cerevisiae. Being a pathway-specific rather than a target-driven assay, we identified small molecule modulators that acted at key steps of autophagic flux. Two of the inhibitors, Bay11 and ZPCK, obtained from the screen were further characterized using secondary assays in yeast. Bay11 inhibited autophagy at a step before fusion with the vacuole whereas ZPCK inhibited the cargo degradation inside the vacuole. Furthermore, we demonstrated that these molecules altered the process of autophagy in mammalian cells as well. Strikingly, these molecules also modulated autophagic flux in a novel model plant, Aponogeton madagascariensis. Thus, using small molecule modulators identified by using a newly developed HTS autophagy assay, our results support that macroautophagy is a conserved process across fungal, animal and plant kingdoms.     

Autophagy and Cancer Therapy

Autophagy is a dynamic process of protein degradation which is typically observed during nutrient deprivation. Recently, interest in autophagy has been renewed among oncologists, because different types of cancer cells undergo autophagy after various anticancer therapies. This type of non-apoptotic cell death has been documented mainly by observing morphological changes, e.g., numerous autophagic vacuoles in the cytoplasm of dying cells. Thus, autophagic cell death is considered programmed cell death type II, whereas apoptosis is programmed cell death type I. These two types of cell death are predominantly distinctive, but many studies demonstrate cross-talk between them. Whether autophagy in cancer cells causes death or protects cells is controversial. In multiple studies, autophagy has been inhibited pharmacologically or genetically, resulting in contrasting outcomes—survival or death—depending on the specific context. Interestingly, the regulatory pathways of autophagy share several molecules with the oncogenic pathways activated by tyrosine kinase receptors. Tumor suppressors such as Beclin 1, PTEN, and p53 also play an important role in autophagy induction. Taken together, these accumulating data may lead to development of new cancer therapies that manipulate autophagy.     

Apoptosis, autophagy, and more

Cell death has been subdivided into the categories apoptosis (Type I), autophagic cell death (Type II), and necrosis (Type III). The boundary between Type I and II has never been completely clear and perhaps does not exist due to intrinsic factors among different cell types and the crosstalk among organelles within each type. Apoptosis can begin with autophagy, autophagy can end with apoptosis, and blockage of caspase activity can cause a cell to default to Type II cell death from Type I. Furthermore, autophagy is a normal physiological process active in both homeostasis (organelle turnover) and atrophy. “Autophagic cell death” may be interpreted as the process of autophagy that, unlike other situations, does not terminate before the cell collapses. Since switching among the alternative pathways to death is relatively common, interpretations based on knockouts or inhibitors, and therapies directed at controlling apoptosis must include these considerations.