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  1. Article ; Online: Regulation and Functions of Autophagy During Animal Development.

    Restrepo, Lucas J / Baehrecke, Eric H

    Journal of molecular biology

    2024  , Page(s) 168473

    Abstract: Autophagy is used to degrade cytoplasmic materials, and is critical to maintain cell and organismal health in diverse animals. Here we discuss the regulation, utilization and impact of autophagy on development, including roles in oogenesis, ... ...

    Abstract Autophagy is used to degrade cytoplasmic materials, and is critical to maintain cell and organismal health in diverse animals. Here we discuss the regulation, utilization and impact of autophagy on development, including roles in oogenesis, spermatogenesis and embryogenesis in animals. We also describe how autophagy influences postembryonic development in the context of neuronal and cardiac development, wound healing, and tissue regeneration. We describe recent studies of selective autophagy during development, including mitochondria-selective autophagy and endoplasmic reticulum (ER)-selective autophagy. Studies of developing model systems have also been used to discover novel regulators of autophagy, and we explain how studies of autophagy in these physiologically relevant systems are advancing our understanding of this important catabolic process.
    Language English
    Publishing date 2024-02-02
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 80229-3
    ISSN 1089-8638 ; 0022-2836
    ISSN (online) 1089-8638
    ISSN 0022-2836
    DOI 10.1016/j.jmb.2024.168473
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    Zs.A 867: Show issues Location:
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  2. Article ; Online: Mass isolation of staged Drosophila pupal intestines for analysis of protein ubiquitylation.

    Wang, Ruoxi / Velentzas, Panagiotis D / Baehrecke, Eric H

    STAR protocols

    2023  Volume 4, Issue 4, Page(s) 102713

    Abstract: Large quantities of developmentally synchronized pupal intestines are required for biochemistry experiments. Here, we present a protocol for the mass isolation of staged pupal intestines during Drosophila melanogaster development based on buoyancy in ... ...

    Abstract Large quantities of developmentally synchronized pupal intestines are required for biochemistry experiments. Here, we present a protocol for the mass isolation of staged pupal intestines during Drosophila melanogaster development based on buoyancy in sucrose for biochemical evaluation of protein ubiquitylation. We describe steps for crossing flies, preparation of samples, immunoprecipitation of proteins from staged isolated tissues, and analysis of samples by western blot. This protocol can be extended to investigate biochemical changes in other tissues. For complete details on the use and execution of this protocol, please refer to Wang et al. (2023).
    MeSH term(s) Animals ; Drosophila ; Drosophila melanogaster ; Ubiquitination ; Blotting, Western ; Intestines ; Pupa
    Language English
    Publishing date 2023-11-11
    Publishing country United States
    Document type Journal Article
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2023.102713
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Histological assessment of developmental cell death in

    Velentzas, Panagiotis D / Baehrecke, Eric H

    STAR protocols

    2021  Volume 2, Issue 2, Page(s) 100473

    Abstract: This protocol describes the embedding and processing ... ...

    Abstract This protocol describes the embedding and processing of
    MeSH term(s) Animals ; Cell Death/physiology ; Drosophila/embryology ; Female ; Histological Techniques/methods ; Larva/cytology ; Male ; Pupa/cytology ; Salivary Glands/cytology
    Language English
    Publishing date 2021-04-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2021.100473
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Autophagy in animal development.

    Allen, Elizabeth A / Baehrecke, Eric H

    Cell death and differentiation

    2020  Volume 27, Issue 3, Page(s) 903–918

    Abstract: Macroautophagy (autophagy) delivers intracellular constituents to the lysosome to promote catabolism. During development in multiple organisms, autophagy mediates various cellular processes, including survival during starvation, programmed cell death, ... ...

    Abstract Macroautophagy (autophagy) delivers intracellular constituents to the lysosome to promote catabolism. During development in multiple organisms, autophagy mediates various cellular processes, including survival during starvation, programmed cell death, phagocytosis, organelle elimination, and miRNA regulation. Our current understanding of autophagy has been enhanced by developmental biology research during the last quarter of a century. Through experiments that focus on animal development, fundamental mechanisms that control autophagy and that contribute to disease were elucidated. Studies in embryos revealed specific autophagy molecules that mediate the removal of paternally derived mitochondria, and identified autophagy components that clear protein aggregates during development. Importantly, defects in mtDNA inheritance, or removal of paternal mtDNA via mitochondrial autophagy, can contribute to mitochondrial-associated disease. In addition, impairment of the clearance of protein aggregates by autophagy underlies neurodegenerative diseases. Experiments in multiple organisms also reveal conserved mechanisms of tissue remodeling that rely on the cooperation between autophagy and apoptosis to clear cell corpses, and defects in autophagy and apoptotic cell clearance can contribute to inflammation and autoimmunity. Here we provide an overview of key developmental processes that are mediated by autophagy in multiple animals.
    MeSH term(s) Animals ; Apoptosis/genetics ; Autophagy/genetics ; Embryonic Development/genetics ; Metamorphosis, Biological/genetics ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Regeneration/genetics
    Chemical Substances MicroRNAs
    Language English
    Publishing date 2020-01-27
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1225672-9
    ISSN 1476-5403 ; 1350-9047
    ISSN (online) 1476-5403
    ISSN 1350-9047
    DOI 10.1038/s41418-020-0497-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Life, death and autophagy.

    Doherty, Johnna / Baehrecke, Eric H

    Nature cell biology

    2018  Volume 20, Issue 10, Page(s) 1110–1117

    Abstract: Autophagy influences cell survival through maintenance of cell bioenergetics and clearance of protein aggregates and damaged organelles. Several lines of evidence indicate that autophagy is a multifaceted regulator of cell death, but controversy exists ... ...

    Abstract Autophagy influences cell survival through maintenance of cell bioenergetics and clearance of protein aggregates and damaged organelles. Several lines of evidence indicate that autophagy is a multifaceted regulator of cell death, but controversy exists over whether autophagy alone can drive cell death under physiologically relevant circumstances. Here, we review the role of autophagy in cell death and examine how autophagy interfaces with other forms of cell death including apoptosis and necrosis.
    MeSH term(s) Animals ; Apoptosis/physiology ; Autophagy/physiology ; Autophagy-Related Proteins/metabolism ; Caspases/metabolism ; Cell Death/physiology ; Cell Survival/physiology ; Humans ; Models, Biological ; Necrosis
    Chemical Substances Autophagy-Related Proteins ; Caspases (EC 3.4.22.-)
    Language English
    Publishing date 2018-09-17
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1474722-4
    ISSN 1476-4679 ; 1465-7392
    ISSN (online) 1476-4679
    ISSN 1465-7392
    DOI 10.1038/s41556-018-0201-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Drosophila E93 promotes adult development and suppresses larval responses to ecdysone during metamorphosis

    Lam, Geanette / Nam, Hyuck-Jin / Velentzas, Panagiotis D. / Baehrecke, Eric H. / Thummel, Carl S.

    Developmental biology. 2022 Jan., v. 481

    2022  

    Abstract: Pulses of the steroid hormone ecdysone act through transcriptional cascades to direct the major developmental transitions during the Drosophila life cycle. These include the prepupal ecdysone pulse, which occurs 10 ​hours after pupariation and triggers ... ...

    Abstract Pulses of the steroid hormone ecdysone act through transcriptional cascades to direct the major developmental transitions during the Drosophila life cycle. These include the prepupal ecdysone pulse, which occurs 10 ​hours after pupariation and triggers the onset of adult morphogenesis and larval tissue destruction. E93 encodes a transcription factor that is specifically induced by the prepupal pulse of ecdysone, supporting a model proposed by earlier work that it specifies the onset of adult development. Although a number of studies have addressed these functions for E93, little is known about its roles in the salivary gland where the E93 locus was originally identified. Here we show that E93 is required for development through late pupal stages, with mutants displaying defects in adult differentiation and no detectable effect on the destruction of larval salivary glands. RNA-seq analysis demonstrates that E93 regulates genes involved in development and morphogenesis in the salivary glands, but has little effect on cell death gene expression. We also show that E93 is required to direct the proper timing of ecdysone-regulated gene expression in salivary glands, and that it suppresses earlier transcriptional programs that occur during larval and prepupal stages. These studies support the model that the stage-specific induction of E93 in late prepupae provides a critical signal that defines the end of larval development and the onset of adult differentiation.
    Keywords Drosophila ; adult development ; adults ; cell death ; ecdysone ; gene expression ; larvae ; larval development ; loci ; models ; morphogenesis ; prepupae ; pupae ; pupariation ; salivary glands ; sequence analysis ; steroid hormones ; transcription (genetics) ; transcription factors
    Language English
    Dates of publication 2022-01
    Size p. 104-115.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1114-9
    ISSN 1095-564X ; 0012-1606
    ISSN (online) 1095-564X
    ISSN 0012-1606
    DOI 10.1016/j.ydbio.2021.10.001
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Vps13D functions in a Pink1-dependent and Parkin-independent mitophagy pathway.

    Shen, James L / Fortier, Tina M / Wang, Ruoxi / Baehrecke, Eric H

    The Journal of cell biology

    2021  Volume 220, Issue 11

    Abstract: Defects in autophagy cause problems in metabolism, development, and disease. The autophagic clearance of mitochondria, mitophagy, is impaired by the loss of Vps13D. Here, we discover that Vps13D regulates mitophagy in a pathway that depends on the core ... ...

    Abstract Defects in autophagy cause problems in metabolism, development, and disease. The autophagic clearance of mitochondria, mitophagy, is impaired by the loss of Vps13D. Here, we discover that Vps13D regulates mitophagy in a pathway that depends on the core autophagy machinery by regulating Atg8a and ubiquitin localization. This process is Pink1 dependent, with loss of pink1 having similar autophagy and mitochondrial defects as loss of vps13d. The role of Pink1 has largely been studied in tandem with Park/Parkin, an E3 ubiquitin ligase that is widely considered to be crucial in Pink1-dependent mitophagy. Surprisingly, we find that loss of park does not exhibit the same autophagy and mitochondrial deficiencies as vps13d and pink1 mutant cells and contributes to mitochondrial clearance through a pathway that is parallel to vps13d. These findings provide a Park-independent pathway for Pink1-regulated mitophagy and help to explain how Vps13D regulates autophagy and mitochondrial morphology and contributes to neurodegenerative diseases.
    MeSH term(s) Animals ; Autophagy/physiology ; Drosophila Proteins/metabolism ; Drosophila melanogaster/metabolism ; Mitochondria/metabolism ; Mitophagy/physiology ; Protein Serine-Threonine Kinases/metabolism ; Signal Transduction/physiology ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/metabolism
    Chemical Substances Drosophila Proteins ; Ubiquitin ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; PINK1 protein, Drosophila (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; park protein, Drosophila (EC 6.3.2.-)
    Language English
    Publishing date 2021-08-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.202104073
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Atg6 promotes organismal health by suppression of cell stress and inflammation.

    Shen, James L / Doherty, Johnna / Allen, Elizabeth / Fortier, Tina M / Baehrecke, Eric H

    Cell death and differentiation

    2022  Volume 29, Issue 11, Page(s) 2275–2287

    Abstract: Autophagy targets cytoplasmic materials for degradation, and influences cell health. Alterations in Atg6/Beclin-1, a key regulator of autophagy, are associated with multiple diseases. While the role of Atg6 in autophagy regulation is heavily studied, the ...

    Abstract Autophagy targets cytoplasmic materials for degradation, and influences cell health. Alterations in Atg6/Beclin-1, a key regulator of autophagy, are associated with multiple diseases. While the role of Atg6 in autophagy regulation is heavily studied, the role of Atg6 in organism health and disease progression remains poorly understood. Here, we discover that loss of Atg6 in Drosophila results in various alterations to stress, metabolic and immune signaling pathways. We find that the increased levels of circulating blood cells and tumor-like masses in atg6 mutants vary depending on tissue-specific function of Atg6, with contributions from intestine and hematopoietic cells. These phenotypes are suppressed by decreased function of macrophage and inflammatory response receptors crq and drpr. Thus, these findings provide a basis for understanding how Atg6 systemically regulates cell health within multiple organs, and highlight the importance of Atg6 in inflammation to organismal health.
    MeSH term(s) Humans ; Beclin-1/metabolism ; Autophagy/genetics ; Signal Transduction ; Inflammation
    Chemical Substances Beclin-1
    Language English
    Publishing date 2022-05-06
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1225672-9
    ISSN 1476-5403 ; 1350-9047
    ISSN (online) 1476-5403
    ISSN 1350-9047
    DOI 10.1038/s41418-022-01014-y
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  9. Article ; Online: ESCRT dysfunction compromises endoplasmic reticulum maturation and autophagosome biogenesis in Drosophila.

    Wang, Ruoxi / Miao, Guangyan / Shen, James L / Fortier, Tina M / Baehrecke, Eric H

    Current biology : CB

    2022  Volume 32, Issue 6, Page(s) 1262–1274.e4

    Abstract: Autophagy targets cytoplasmic materials for degradation and influences cell health. Organelle contact and trafficking systems provide membranes for autophagosome formation, but how different membrane systems are selected for use during autophagy remains ... ...

    Abstract Autophagy targets cytoplasmic materials for degradation and influences cell health. Organelle contact and trafficking systems provide membranes for autophagosome formation, but how different membrane systems are selected for use during autophagy remains unclear. Here, we report a novel function of the endosomal sorting complex required for transport (ESCRT) in the regulation of endoplasmic reticulum (ER) coat protein complex II (COPII) vesicle formation that influences autophagy. The ESCRT functions in a pathway upstream of Vps13D to influence COPII vesicle transport, ER-Golgi intermediate compartment (ERGIC) assembly, and autophagosome formation. Atg9 functions downstream of the ESCRT to facilitate ERGIC and autophagosome formation. Interestingly, cells lacking either ESCRT or Vps13D functions exhibit dilated ER structures that are similar to cranio-lenticulo-sutural dysplasia patient cells with SEC23A mutations, which encodes a component of COPII vesicles. Our data reveal a novel ESCRT-dependent pathway that influences the ERGIC and autophagosome formation.
    MeSH term(s) Animals ; Autophagosomes/metabolism ; Autophagy/physiology ; Autophagy-Related Proteins/genetics ; Autophagy-Related Proteins/metabolism ; Drosophila/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Endoplasmic Reticulum/metabolism ; Endosomal Sorting Complexes Required for Transport/genetics ; Endosomal Sorting Complexes Required for Transport/metabolism ; Golgi Apparatus/metabolism ; Humans ; Membrane Proteins/metabolism ; Protein Transport/physiology ; Proteins/metabolism
    Chemical Substances Atg9 protein, Drosophila ; Autophagy-Related Proteins ; Drosophila Proteins ; Endosomal Sorting Complexes Required for Transport ; Membrane Proteins ; Proteins ; VPS13D protein, human
    Language English
    Publishing date 2022-02-07
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2022.01.040
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  10. Article ; Online: Cleaning House: Selective Autophagy of Organelles.

    Anding, Allyson L / Baehrecke, Eric H

    Developmental cell

    2017  Volume 41, Issue 1, Page(s) 10–22

    Abstract: The selective clearance of organelles by autophagy is critical for the regulation of cellular homeostasis in organisms from yeast to humans. Removal of damaged organelles clears the cell of potentially toxic byproducts and enables reuse of organelle ... ...

    Abstract The selective clearance of organelles by autophagy is critical for the regulation of cellular homeostasis in organisms from yeast to humans. Removal of damaged organelles clears the cell of potentially toxic byproducts and enables reuse of organelle components for bioenergetics. Thus, defects in organelle clearance may be detrimental to the health of the cells, contributing to cancer, neurodegeneration, and inflammatory diseases. Organelle-specific autophagy can clear mitochondria, peroxisomes, lysosomes, ER, chloroplasts, and the nucleus. Here, we review our understanding of the mechanisms that regulate the clearance of organelles by autophagy and highlight gaps in our knowledge of these processes.
    MeSH term(s) Animals ; Autophagy ; Humans ; Mitochondrial Degradation ; Models, Biological ; Organelles/metabolism
    Language English
    Publishing date 2017-04-10
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2017.02.016
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