Methods to Study Autophagy in Zebrafish

Fodor, Erika; Sigmond, Tímea; Ari, Eszter; Lengyel, Katalin; Takács‐Vellai, Krisztina; Varga, Máté; Vellai, Tibor

doi:10.1016/bs.mie.2016.10.028

Cited by 17 publications

(8 citation statements)

References 81 publications

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“…Prior to this life period, cellular damages are effectively degraded (i.e. eliminated) by the repair and maintenance processes and mechanisms including autophagy (cellular self-eating) being the most significant form of breaking down cytoplasmic materials 49 , 50 , the ubiquitin-proteasome system and molecular chaperons, also called heat-shock proteins, as well as the DNA repair pathways. These processes and mechanisms, however, display a gradual decline in their capacity as the organism ages.…”

Section: Discussionmentioning

confidence: 99%

Prediction and characterization of human ageing-related proteins by using machine learning

Kerepesi

Daróczy

Sturm

et al. 2018

Sci Rep

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Ageing has a huge impact on human health and economy, but its molecular basis – regulation and mechanism – is still poorly understood. By today, more than three hundred genes (almost all of them function as protein-coding genes) have been related to human ageing. Although individual ageing-related genes or some small subsets of these genes have been intensively studied, their analysis as a whole has been highly limited. To fill this gap, for each human protein we extracted 21000 protein features from various databases, and using these data as an input to state-of-the-art machine learning methods, we classified human proteins as ageing-related or non-ageing-related. We found a simple classification model based on only 36 protein features, such as the “number of ageing-related interaction partners”, “response to oxidative stress”, “damaged DNA binding”, “rhythmic process” and “extracellular region”. Predicted values of the model quantify the relevance of a given protein in the regulation or mechanisms of the human ageing process. Furthermore, we identified new candidate proteins having strong computational evidence of their important role in ageing. Some of them, like Cytochrome b-245 light chain (CY24A) and Endoribonuclease ZC3H12A (ZC12A) have no previous ageing-associated annotations.

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Section: Discussionmentioning

confidence: 99%

Prediction and characterization of human ageing-related proteins by using machine learning

Kerepesi

Daróczy

Sturm

et al. 2018

Sci Rep

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“…Understanding how autophagy modulation helps to promote myocardial regeneration may lead to alternative therapeutic targets for humans to assist in myocardial infarction recovery and the treatment of other chronic cardiovascular diseases. Since the current availability of genetic tools are allowing the zebrafish to become an advantageous model for the study of autophagy 25,67 , future studies will be able to address the precise mechanisms and consequences of autophagy activation upon cardiac injury based on it.…”

Section: Scientific Reports |mentioning

confidence: 99%

Autophagy Activation in Zebrafish Heart Regeneration

Chávez

Morales

López-Crisosto

et al. 2020

Sci Rep

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Autophagy is an evolutionarily conserved process that plays a key role in the maintenance of overall cellular health. While it has been suggested that autophagy may elicit cardioprotective and pro-survival modulating functions, excessive activation of autophagy can also be detrimental. In this regard, the zebrafish is considered a hallmark model for vertebrate regeneration, since contrary to adult mammals, it is able to faithfully regenerate cardiac tissue. Interestingly, the role that autophagy may play in zebrafish heart regeneration has not been studied yet. In the present work, we hypothesize that, in the context of a well-established injury model of ventricular apex resection, autophagy plays a critical role during cardiac regeneration and its regulation can directly affect the zebrafish regenerative potential. We studied the autophagy events occurring upon injury using electron microscopy, in vivo tracking of autophagy markers, and protein analysis. Additionally, using pharmacological tools, we investigated how rapamycin, an inducer of autophagy, affects regeneration relevant processes. Our results show that a tightly regulated autophagic response is triggered upon injury and during the early stages of the regeneration process. Furthermore, treatment with rapamycin caused an impairment in the cardiac regeneration outcome. These findings are reminiscent of the pathophysiological description of an injured human heart and hence put forward the zebrafish as a model to study the poorly understood double-sword effect that autophagy has in cardiac homeostasis.Autophagy is an evolutionarily conserved self-degradation process that involves the engulfment, degradation and recycling of dysfunctional or damaged cellular components 1 . It assumes key roles during adaptation to nutrient starvation 1,2 elimination of pathogens 3 , while it is fundamental in cell differentiation and tissue patterning during development 4 and regeneration 5-7 . In the heart, autophagy has been found to be essential for cardiac development, morphogenesis and cardiomyocyte differentiation 8-10 , and is recognized as a highly relevant housekeeping mechanism for the maintenance of the post-mitotic, essentially unreplaceable, cardiomyocytes that constitute it 11 . On the other hand, autophagy has been found to be involved in the onset and progression of many cardiovascular diseases, such as myocardial infarction and chronic heart failure, where it is a riddle how autophagy may have a protective role, while at the same time, aggravating cardiac dysfunction 12,13 . Because of this, autophagy has been recognized as a potential therapeutic target for cardiovascular diseases, though finding the right strategy to use autophagy activation to improve clinical outcome has not been possible until now 14,15 .The zebrafish (Danio rerio) has become a popular vertebrate model organism because of its superb regenerative capacities. Experimental models of heart amputation 16 , cardiomyocyte-specific genetic ablation 17 , hypoxic damage and ischemia/reperfusion ...

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“…The role of autophagy in survival of hematopoietic cells was observed in a disrupted ribosome biogenesis model of zebrafish where rps19 was ablated using translation morpholino [ 75 , 76 ]. A detailed list of all morpholinos used to analyze autophagy in zebrafish has been included in another review [ 77 ].…”

Section: Genome Editing Techniquesmentioning

confidence: 99%

“…It is however important to note that increased mRNA levels of autophagic genes should not be interpreted as increased autophagy, as it can be a compensatory mechanism. A detailed list of primers used to assess the expression of autophagy-related genes by quantitative real-time PCR (qRT-PCR) in zebrafish has been reviewed recently [ 77 ]. Zebrafish embryos and larvae are also very suited for whole mount in situ hybridization (WISH), which provides information about the spatial expression of a particular gene in the whole organism.…”

Section: Rna-based Analysismentioning

confidence: 99%

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Studying Autophagy in Zebrafish

Mathai

Meijer

Simonsen

2017

Cells

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Autophagy is an evolutionarily conserved catabolic process which allows lysosomal degradation of complex cytoplasmic components into basic biomolecules that are recycled for further cellular use. Autophagy is critical for cellular homeostasis and for degradation of misfolded proteins and damaged organelles as well as intracellular pathogens. The role of autophagy in protection against age-related diseases and a plethora of other diseases is now coming to light; assisted by several divergent eukaryotic model systems ranging from yeast to mice. We here give an overview of different methods used to analyse autophagy in zebrafish—a relatively new model for studying autophagy—and briefly discuss what has been done so far and possible future directions.

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Methods to Study Autophagy in Zebrafish

Cited by 17 publications

References 81 publications

Prediction and characterization of human ageing-related proteins by using machine learning

Prediction and characterization of human ageing-related proteins by using machine learning

Autophagy Activation in Zebrafish Heart Regeneration

Studying Autophagy in Zebrafish

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