Cargando…
Noncanonical necrosis in 2 different cell types in a Caenorhabditis elegans NAD(+) salvage pathway mutant
Necrosis was once described as a chaotic unregulated response to cellular insult. We now know that necrosis is controlled by multiple pathways in response to many different cellular conditions. In our pnc-1 NAD(+) salvage deficient Caenorhabditis elegans model excess nicotinamide induces excitotoxic...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982427/ https://www.ncbi.nlm.nih.gov/pubmed/35143646 http://dx.doi.org/10.1093/g3journal/jkac033 |
_version_ | 1784681809387192320 |
---|---|
author | Reza, Rifath N Serra, Nicholas D Detwiler, Ariana C Hanna-Rose, Wendy Crook, Matt |
author_facet | Reza, Rifath N Serra, Nicholas D Detwiler, Ariana C Hanna-Rose, Wendy Crook, Matt |
author_sort | Reza, Rifath N |
collection | PubMed |
description | Necrosis was once described as a chaotic unregulated response to cellular insult. We now know that necrosis is controlled by multiple pathways in response to many different cellular conditions. In our pnc-1 NAD(+) salvage deficient Caenorhabditis elegans model excess nicotinamide induces excitotoxic death in uterine-vulval uv1 cells and OLQ mechanosensory neurons. We sought to characterize necrosis in our pnc-1 model in the context of well-characterized necrosis, apoptosis, and autophagy pathways in C. elegans. We confirmed that calpain and aspartic proteases were required for uv1 necrosis, but changes in intracellular calcium levels and autophagy were not, suggesting that uv1 necrosis occurs by a pathway that diverges from mec-4d-induced touch cell necrosis downstream of effector aspartic proteases. OLQ necrosis does not require changes in intracellular calcium, the function of calpain or aspartic proteases, or autophagy. Instead, OLQ survival requires the function of calreticulin and calnexin, pro-apoptotic ced-4 (Apaf1), and genes involved in both autophagy and axon guidance. In addition, the partially OLQ-dependent gentle nose touch response decreased significantly in pnc-1 animals on poor quality food, further suggesting that uv1 and OLQ necrosis differ downstream of their common trigger. Together these results show that, although phenotypically very similar, uv1, OLQ, and touch cell necrosis are very different at the molecular level. |
format | Online Article Text |
id | pubmed-8982427 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-89824272022-04-05 Noncanonical necrosis in 2 different cell types in a Caenorhabditis elegans NAD(+) salvage pathway mutant Reza, Rifath N Serra, Nicholas D Detwiler, Ariana C Hanna-Rose, Wendy Crook, Matt G3 (Bethesda) Investigation Necrosis was once described as a chaotic unregulated response to cellular insult. We now know that necrosis is controlled by multiple pathways in response to many different cellular conditions. In our pnc-1 NAD(+) salvage deficient Caenorhabditis elegans model excess nicotinamide induces excitotoxic death in uterine-vulval uv1 cells and OLQ mechanosensory neurons. We sought to characterize necrosis in our pnc-1 model in the context of well-characterized necrosis, apoptosis, and autophagy pathways in C. elegans. We confirmed that calpain and aspartic proteases were required for uv1 necrosis, but changes in intracellular calcium levels and autophagy were not, suggesting that uv1 necrosis occurs by a pathway that diverges from mec-4d-induced touch cell necrosis downstream of effector aspartic proteases. OLQ necrosis does not require changes in intracellular calcium, the function of calpain or aspartic proteases, or autophagy. Instead, OLQ survival requires the function of calreticulin and calnexin, pro-apoptotic ced-4 (Apaf1), and genes involved in both autophagy and axon guidance. In addition, the partially OLQ-dependent gentle nose touch response decreased significantly in pnc-1 animals on poor quality food, further suggesting that uv1 and OLQ necrosis differ downstream of their common trigger. Together these results show that, although phenotypically very similar, uv1, OLQ, and touch cell necrosis are very different at the molecular level. Oxford University Press 2022-02-10 /pmc/articles/PMC8982427/ /pubmed/35143646 http://dx.doi.org/10.1093/g3journal/jkac033 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Investigation Reza, Rifath N Serra, Nicholas D Detwiler, Ariana C Hanna-Rose, Wendy Crook, Matt Noncanonical necrosis in 2 different cell types in a Caenorhabditis elegans NAD(+) salvage pathway mutant |
title | Noncanonical necrosis in 2 different cell types in a Caenorhabditis elegans NAD(+) salvage pathway mutant |
title_full | Noncanonical necrosis in 2 different cell types in a Caenorhabditis elegans NAD(+) salvage pathway mutant |
title_fullStr | Noncanonical necrosis in 2 different cell types in a Caenorhabditis elegans NAD(+) salvage pathway mutant |
title_full_unstemmed | Noncanonical necrosis in 2 different cell types in a Caenorhabditis elegans NAD(+) salvage pathway mutant |
title_short | Noncanonical necrosis in 2 different cell types in a Caenorhabditis elegans NAD(+) salvage pathway mutant |
title_sort | noncanonical necrosis in 2 different cell types in a caenorhabditis elegans nad(+) salvage pathway mutant |
topic | Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982427/ https://www.ncbi.nlm.nih.gov/pubmed/35143646 http://dx.doi.org/10.1093/g3journal/jkac033 |
work_keys_str_mv | AT rezarifathn noncanonicalnecrosisin2differentcelltypesinacaenorhabditiselegansnadsalvagepathwaymutant AT serranicholasd noncanonicalnecrosisin2differentcelltypesinacaenorhabditiselegansnadsalvagepathwaymutant AT detwilerarianac noncanonicalnecrosisin2differentcelltypesinacaenorhabditiselegansnadsalvagepathwaymutant AT hannarosewendy noncanonicalnecrosisin2differentcelltypesinacaenorhabditiselegansnadsalvagepathwaymutant AT crookmatt noncanonicalnecrosisin2differentcelltypesinacaenorhabditiselegansnadsalvagepathwaymutant |