title: Shared developmental roles and transcriptional control of autophagy and apoptosis in Caenorhabditis elegans.
abstract: Autophagy is a lysosome-mediated self-degradation process of eukaryotic cells that, depending on the cellular milieu, can either promote survival or act as an alternative mechanism of programmed cell death (PCD) in terminally differentiated cells. Despite the important developmental and medical implications of autophagy and the main form of PCD, apoptosis, orchestration of their regulation remains poorly understood. Here, we show in the nematode Caenorhabditis elegans, that various genetic and pharmacological interventions causing embryonic lethality trigger a massive cell death response that has both autophagic and apoptotic features. The two degradation processes are also redundantly required for normal development and viability in this organism. Furthermore, the CES-2-like basic region leucine-zipper (bZip) transcription factor ATF-2, an upstream modulator of the core apoptotic cell death pathway, is able to directly regulate the expression of at least two key autophagy-related genes, bec-1/ATG6 and lgg-1/ATG8. Thus, the two cell death mechanisms share a common method of transcriptional regulation. Together, these results imply that under certain physiological and pathological conditions, autophagy and apoptosis are co-regulated to ensure the proper morphogenesis and survival of the developing organism. The identification of apoptosis and autophagy as compensatory cellular pathways in C. elegans might help us to understand how dysregulated PCD in humans can lead to diverse pathologies, including cancer, neurodegeneration and diabetes.
authors.affiliation: Department of Genetics, Eötvös Loránd University, Budapest H-1117, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Erdélyi
authors.forename: Eva
authors.initials: E
authors.lastname: Borsos
authors.forename: Krisztina
authors.initials: K
authors.lastname: Takács-Vellai
authors.forename: Tibor
authors.initials: T
authors.lastname: Kovács
authors.forename: Attila L
authors.initials: AL
authors.lastname: Kovács
authors.forename: Tímea
authors.initials: T
authors.lastname: Sigmond
authors.forename: Balázs
authors.initials: B
authors.lastname: Hargitai
authors.forename: Líz
authors.initials: L
authors.lastname: Pásztor
authors.forename: Tanima
authors.initials: T
authors.lastname: Sengupta
authors.forename: Marlene
authors.initials: M
authors.lastname: Dengg
authors.forename: Ildikó
authors.initials: I
authors.lastname: Pécsi
authors.forename: Judit
authors.initials: J
authors.lastname: Tóth
authors.forename: Hilde
authors.initials: H
authors.lastname: Nilsen
authors.forename: Beáta G
authors.initials: BG
authors.lastname: Vértessy
authors.forename: Tibor
authors.initials: T
authors.lastname: Vellai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D033921:Vesicular Transport Proteins; C477268:bec-1 protein, C elegans