skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


This content will become publicly available on April 1, 2026

Title: Conserved components of the macroautophagy machinery in Caenorhabditis elegans
Abstract Macroautophagy involves the sequestration of cytoplasmic contents in a double-membrane autophagosome and its subsequent delivery to lysosomes for degradation and recycling. In Caenorhabditis elegans, autophagy participates in diverse processes such as stress resistance, cell fate specification, tissue remodeling, aging, and adaptive immunity. Genetic screens in C. elegans have identified a set of metazoan-specific autophagy genes that form the basis for our molecular understanding of steps unique to the autophagy pathway in multicellular organisms. Suppressor screens have uncovered multiple mechanisms that modulate autophagy activity under physiological conditions. C. elegans also provides a model to investigate how autophagy activity is coordinately controlled at an organismal level. In this chapter, we will discuss the molecular machinery, regulation, and physiological functions of autophagy, and also methods utilized for monitoring autophagy during C. elegans development.  more » « less
Award ID(s):
2223241 2215946
PAR ID:
10632664
Author(s) / Creator(s):
;
Editor(s):
Greenwald, I
Publisher / Repository:
Oxford
Date Published:
Journal Name:
GENETICS
Volume:
229
Issue:
4
ISSN:
1943-2631
Subject(s) / Keyword(s):
autophagy macroautophagy
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract The nematode Caenorhabditis elegans has been central to the understanding of metazoan biology. However, C. elegans is but one species among millions and the significance of this important model organism will only be fully revealed if it is placed in a rich evolutionary context. Global sampling efforts have led to the discovery of over 50 putative species from the genus Caenorhabditis, many of which await formal species description. Here, we present species descriptions for 10 new Caenorhabditis species. We also present draft genome sequences for nine of these new species, along with a transcriptome assembly for one. We exploit these whole-genome data to reconstruct the Caenorhabditis phylogeny and use this phylogenetic tree to dissect the evolution of morphology in the genus. We reveal extensive variation in genome size and investigate the molecular processes that underlie this variation. We show unexpected complexity in the evolutionary history of key developmental pathway genes. These new species and the associated genomic resources will be essential in our attempts to understand the evolutionary origins of the C. elegans model. 
    more » « less
  2. Abstract Orsay virus infection in the nematodeCaenorhabditis eleganspresents an opportunity to study host‐virus interactions in an easily culturable, whole‐animal host. Previously, a major limitation ofC. elegansas a model for studying antiviral immunity was the lack of viruses known to naturally infect the worm. With the 2011 discovery of the Orsay virus, a naturally occurring viral pathogen,C. eleganshas emerged as a compelling model for research on antiviral defense. From the perspective of the host, the genetic tractability ofC. elegansenables mechanistic studies of antiviral immunity while the transparency of this animal allows for the observation of subcellular processes in vivo. Preparing infective virus filtrate and performing infections can be achieved with relative ease in a laboratory setting. Moreover, several tools are available to measure the outcome of infection. Here, we describe workflows for generating infective virus filtrate, achieving reproducible infection ofC. elegans, and assessing the outcome of viral infection using molecular biology approaches and immunofluorescence. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Preparation of Orsay virus filtrate Support Protocol: SynchronizeC. elegansdevelopment by bleaching Basic Protocol 2: Orsay virus infection Basic Protocol 3: Quantification of Orsay virus RNA1/RNA2 transcript levels by qRT‐PCR Basic Protocol 4: Quantification of infection rate and fluorescence in situ hybridization (FISH) fluorescence intensity Basic Protocol 5: Immunofluorescent labeling of dsRNA in virus‐infected intestinal tissue 
    more » « less
  3. Abstract In plants, autophagy is a conserved process by which intracellular materials, including damaged proteins, aggregates, and entire organelles, are trafficked to the vacuole for degradation, thus maintaining cellular homeostasis. The past few decades have seen extensive research into the core components of the central autophagy machinery and their physiological roles in plant growth and development as well as responses to biotic and abiotic stresses. Moreover, several methods have been established for monitoring autophagic activities in plants, and these have greatly facilitated plant autophagy research. However, some of the methodologies are prone to misuse or misinterpretation, sometimes casting doubt on the reliability of the conclusions being drawn about plant autophagy. Here, we summarize the methods that are widely used for monitoring plant autophagy at the physiological, microscopic, and biochemical levels, including discussions of their advantages and limitations, to provide a guide for studying this important process. 
    more » « less
  4. Abstract Oxidative protein folding in the endoplasmic reticulum (ER) is essential for all eukaryotic cells yet generates hydrogen peroxide (H2O2), a reactive oxygen species (ROS). The ER-transmembrane protein that provides reducing equivalents to ER and guards the cytosol for antioxidant defense remains unidentified. Here we combine AlphaFold2-based and functional reporter screens inC. elegansto discover a previously uncharacterized and evolutionarily conserved protein ERGU-1 that fulfills these roles. DeletingC. elegansERGU-1 causes excessive H2O2and transcriptional gene up-regulation through SKN-1, homolog of mammalian antioxidant master regulator NRF2. ERGU-1 deficiency also impairs organismal reproduction and behavioral responses to H2O2. BothC. elegansand human ERGU-1 proteins localize to ER membranes and form network reticulum structures. Human andDrosophilahomologs of ERGU-1 can rescueC. elegansmutant phenotypes, demonstrating evolutionarily ancient and conserved functions. In addition, purified ERGU-1 and human homolog TMEM161B exhibit redox-modulated oligomeric states. Together, our results reveal an ER-membrane-specific protein machinery for peroxide detoxification and suggest a previously unknown and conserved mechanisms for antioxidant defense in animal cells. 
    more » « less
  5. Abstract Studies of model organisms have provided important insights into how natural genetic differences shape trait variation. These discoveries are driven by the growing availability of genomes and the expansive experimental toolkits afforded to researchers using these species. For example, Caenorhabditis elegans is increasingly being used to identify and measure the effects of natural genetic variants on traits using quantitative genetics. Since 2016, the C. elegans Natural Diversity Resource (CeNDR) has facilitated many of these studies by providing an archive of wild strains, genome-wide sequence and variant data for each strain, and a genome-wide association (GWA) mapping portal for the C. elegans community. Here, we present an updated platform, the Caenorhabditis Natural Diversity Resource (CaeNDR), that enables quantitative genetics and genomics studies across the three Caenorhabditis species: C. elegans, C. briggsae and C. tropicalis. The CaeNDR platform hosts several databases that are continually updated by the addition of new strains, whole-genome sequence data and annotated variants. Additionally, CaeNDR provides new interactive tools to explore natural variation and enable GWA mappings. All CaeNDR data and tools are accessible through a freely available web portal located at caendr.org. 
    more » « less