Article ; Online: Autophagy protein ATG-16.2 and its WD40 domain mediate the beneficial effects of inhibiting early-acting autophagy genes in C. elegans neurons.
Nature aging
2024 Volume 4, Issue 2, Page(s) 198–212
Abstract: While autophagy genes are required for lifespan of long-lived animals, their tissue-specific roles in aging remain unclear. Here, we inhibited autophagy genes in Caenorhabditis elegans neurons, and found that knockdown of early-acting autophagy genes, ... ...
| Abstract | While autophagy genes are required for lifespan of long-lived animals, their tissue-specific roles in aging remain unclear. Here, we inhibited autophagy genes in Caenorhabditis elegans neurons, and found that knockdown of early-acting autophagy genes, except atg-16.2, increased lifespan, and decreased neuronal PolyQ aggregates, independently of autophagosomal degradation. Neurons can secrete protein aggregates via vesicles called exophers. Inhibiting neuronal early-acting autophagy genes, except atg-16.2, increased exopher formation and exopher events extended lifespan, suggesting exophers promote organismal fitness. Lifespan extension, reduction in PolyQ aggregates and increase in exophers were absent in atg-16.2 null mutants, and restored by full-length ATG-16.2 expression in neurons, but not by ATG-16.2 lacking its WD40 domain, which mediates noncanonical functions in mammalian systems. We discovered a neuronal role for C. elegans ATG-16.2 and its WD40 domain in lifespan, proteostasis and exopher biogenesis. Our findings suggest noncanonical functions for select autophagy genes in both exopher formation and in aging. |
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| MeSH term(s) | Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/genetics ; Longevity/genetics ; Neurons/metabolism ; Autophagy/genetics ; Mammals/metabolism |
| Chemical Substances | Caenorhabditis elegans Proteins |
| Language | English |
| Publishing date | 2024-01-04 |
| Publishing country | United States |
| Document type | Journal Article |
| ISSN | 2662-8465 |
| ISSN (online) | 2662-8465 |
| DOI | 10.1038/s43587-023-00548-1 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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