LPD-3 as a megaprotein brake for aging and insulin-mTOR signaling in C. elegans Article Swipe
Taruna Pandey
,
Bingying Wang
,
Changnan Wang
,
Jenny Zu
,
Huichao Deng
,
Kang Shen
,
Gonçalo Vale
,
Jeffrey G. McDonald
,
K. Dengke
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.celrep.2024.113899
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.celrep.2024.113899
Insulin-mechanistic target of rapamycin (mTOR) signaling drives anabolic growth during organismal development; its late-life dysregulation contributes to aging and limits lifespans. Age-related regulatory mechanisms and functional consequences of insulin-mTOR remain incompletely understood. Here, we identify LPD-3 as a megaprotein that orchestrates the tempo of insulin-mTOR signaling during C. elegans aging. We find that an agonist insulin, INS-7, is drastically overproduced from early life and shortens lifespan in lpd-3 mutants. LPD-3 forms a bridge-like tunnel megaprotein to facilitate non-vesicular cellular lipid trafficking. Lipidomic profiling reveals increased hexaceramide species in lpd-3 mutants, accompanied by up-regulation of hexaceramide biosynthetic enzymes, including HYL-1. Reducing the abundance of HYL-1, insulin receptor/DAF-2 or mTOR/LET-363, normalizes INS-7 levels and rescues the lifespan of lpd-3 mutants. LPD-3 antagonizes SINH-1, a key mTORC2 component, and decreases expression with age. We propose that LPD-3 acts as a megaprotein brake for organismal aging and that its age-dependent decline restricts lifespan through the sphingolipid-hexaceramide and insulin-mTOR pathways.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.celrep.2024.113899
- http://www.cell.com/article/S2211124724002274/pdf
- OA Status
- gold
- Cited By
- 8
- References
- 68
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4392453583
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4392453583Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1016/j.celrep.2024.113899Digital Object Identifier
- Title
-
LPD-3 as a megaprotein brake for aging and insulin-mTOR signaling in C. elegansWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-03-01Full publication date if available
- Authors
-
Taruna Pandey, Bingying Wang, Changnan Wang, Jenny Zu, Huichao Deng, Kang Shen, Gonçalo Vale, Jeffrey G. McDonald, K. DengkeList of authors in order
- Landing page
-
https://doi.org/10.1016/j.celrep.2024.113899Publisher landing page
- PDF URL
-
https://www.cell.com/article/S2211124724002274/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.cell.com/article/S2211124724002274/pdfDirect OA link when available
- Concepts
-
PI3K/AKT/mTOR pathway, Insulin, Insulin receptor, Signal transduction, Cell biology, Caenorhabditis elegans, Chemistry, Endocrinology, Internal medicine, Biology, Medicine, Insulin resistance, Biochemistry, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
8Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 5, 2024: 3Per-year citation counts (last 5 years)
- References (count)
-
68Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| referenced_works_count | 68 |
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| abstract_inverted_index.Here, | 32 |
| abstract_inverted_index.INS-7 | 109 |
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| abstract_inverted_index.mutants. | 68, 117 |
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| corresponding_author_ids | https://openalex.org/A5020931583 |
| countries_distinct_count | 1 |
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| corresponding_institution_ids | https://openalex.org/I180670191, https://openalex.org/I4210109258, https://openalex.org/I95457486 |
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