Protein hunger-driven nitrogen flow from phospholipids to amino acids inDrosophila
- 1University of California, San Francisco, San Francisco
Abstract
Protein is unique among macronutrients due to its nitrogen content and that its building blocks, essential amino acids, cannot be synthesized by animals. Additionally, animals lack specialized amino acid storage sites, necessitating a continuous dietary intake. In the face of insufficient dietary protein, how do animals manage nitrogen limitation? Using Drosophila, we reveal a previously undocumented nitrogen flow from phospholipids to amino acids, a process enhanced by protein deprivation. Protein restriction triggers the degradation of phosphatidylethanolamine (PE), releasing the nitrogen-containing headgroup, ethanolamine, which subsequently serves a dual function. Ethanolamine stimulates protein intake by activating protein hunger neurons and, remarkably, along with phosphoethanolamine, donates nitrogen for amino acid biosynthesis. This nitrogen transfer is mediated by the microbiome and ethanolamine-phosphate phospho-lyase (ETNPPL) pathway in fly cells. Together, our findings identify phospholipids as a hidden nitrogen reservoir and reveal an unrecognized metabolic plasticity that reallocates nitrogen to maintain protein homeostasis.
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BibTeX
@misc{liu2026protein,
title = {{Protein hunger-driven nitrogen flow from phospholipids to amino acids inDrosophila}},
author = {Q. Liu and T. Ma and G. Wu and L. Tham and M. Palarca-Wong and S. Vaz and N. Allen and C. Shao and A. Tsai and R. W. Song and P. M. England},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.18.752762},
url = {https://www.biorxiv.org/content/10.64898/2026.09.18.752762v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Protein hunger-driven nitrogen flow from phospholipids to amino acids inDrosophila
AU - Q. Liu
AU - T. Ma
AU - G. Wu
AU - L. Tham
AU - M. Palarca-Wong
AU - S. Vaz
AU - N. Allen
AU - C. Shao
AU - A. Tsai
AU - R. W. Song
AU - P. M. England
PY - 2026
DA - 2026/09/18
PB - bioRxiv
DO - 10.64898/2026.09.18.752762
UR - https://www.biorxiv.org/content/10.64898/2026.09.18.752762v1
AB - Protein is unique among macronutrients due to its nitrogen content and that its building blocks, essential amino acids, cannot be synthesized by animals. Additionally, animals lack specialized amino acid storage sites, necessitating a continuous dietary intake. In the face of insufficient dietary protein, how do animals manage nitrogen limitation? Using Drosophila, we reveal a previously undocumented nitrogen flow from phospholipids to amino acids, a process enhanced by protein deprivation. Protein restriction triggers the degradation of phosphatidylethanolamine (PE), releasing the nitrogen-containing headgroup, ethanolamine, which subsequently serves a dual function. Ethanolamine stimulates protein intake by activating protein hunger neurons and, remarkably, along with phosphoethanolamine, donates nitrogen for amino acid biosynthesis. This nitrogen transfer is mediated by the microbiome and ethanolamine-phosphate phospho-lyase (ETNPPL) pathway in fly cells. Together, our findings identify phospholipids as a hidden nitrogen reservoir and reveal an unrecognized metabolic plasticity that reallocates nitrogen to maintain protein homeostasis.
ER -