Protein resource allocation across subcellular compartments revealed by large-scale absolute quantitative proteomics in yeast
5 affiliations
- 1State Key Laboratory of Microbial Metabolism, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
- 2Institute of Natural Sciences, School of Mathematical Sciences, Zhangjiang Institute of Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China
- 3Shanghai AI Laboratory, Shanghai 200232, China
- 4BioInnovation Institute, Ole Måløes Vej, Copenhagen N DK2200, Denmark
- 5Department of Life Sciences, Chalmers University of Technology, Gothenburg SE412 96, Sweden
Abstract
Subcellular compartmentalization within complex membrane-bound organelles is a hallmark of eukaryal life, enabling metabolic specialization through spatial segregation. Here, we compiled a dataset encompassing 300 absolute quantitative proteomes, the largest to date, across two yeast species under diverse experimental conditions. Leveraging big data analysis, formula fitting, and machine learning, quantitative correlations among protein abundance, resource allocation, and cellular phenotypes were elucidated at a system level. We found that subcellular resource distribution is highly uneven and covaries with specific growth rate. Specifically, at high specific growth rates, the protein mass fraction (PMF) from certain compartments, (e.g., nucleus) is consistently reduced, coinciding with the increasing protein resource demand from ribosomes. Meanwhile, nutrient limitation may induce resource recycling by upregulating protein resources within specific compartments (e.g., vacuole) to sustain stress adaptation. Importantly, our integrative analysis indicates that PMF from a few subcellular compartments (e.g., nucleus and ribosomes) can accurately predict yeast physiological parameters (e.g., specific growth rate, oxygen uptake rate), and a limited protein set (≥ 23) could be used to capture the variation in resource allocation across seven major subcellular compartments. Furthermore, our comparative analysis between Crabtree-positive and Crabtree-negative species across conditions illustrates that subcellular resource allocation could be shaped by multiple factors and the two species differ markedly in their robustness to environmental perturbations. In summary, the high-quality quantitative proteomic dataset for yeast species offers an unprecedented opportunity for understanding the general principles underlying subcellular resource allocation, laying foundations for precision engineering of cell factories in synthetic biology.
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BibTeX
@article{lu2026protein,
title = {{Protein resource allocation across subcellular compartments revealed by large-scale absolute quantitative proteomics in yeast}},
author = {Hongzhong Lu and Zhendong Zhang and Siwei He and Yucan Zhang and Yuguang Wang and Fei Tao and Jens Nielsen},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2621208123},
url = {https://doi.org/10.1073/pnas.2621208123},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Protein resource allocation across subcellular compartments revealed by large-scale absolute quantitative proteomics in yeast
AU - Hongzhong Lu
AU - Zhendong Zhang
AU - Siwei He
AU - Yucan Zhang
AU - Yuguang Wang
AU - Fei Tao
AU - Jens Nielsen
PY - 2026
DA - 2026/10/27
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2621208123
UR - https://doi.org/10.1073/pnas.2621208123
AB - Subcellular compartmentalization within complex membrane-bound organelles is a hallmark of eukaryal life, enabling metabolic specialization through spatial segregation. Here, we compiled a dataset encompassing 300 absolute quantitative proteomes, the largest to date, across two yeast species under diverse experimental conditions. Leveraging big data analysis, formula fitting, and machine learning, quantitative correlations among protein abundance, resource allocation, and cellular phenotypes were elucidated at a system level. We found that subcellular resource distribution is highly uneven and covaries with specific growth rate. Specifically, at high specific growth rates, the protein mass fraction (PMF) from certain compartments, (e.g., nucleus) is consistently reduced, coinciding with the increasing protein resource demand from ribosomes. Meanwhile, nutrient limitation may induce resource recycling by upregulating protein resources within specific compartments (e.g., vacuole) to sustain stress adaptation. Importantly, our integrative analysis indicates that PMF from a few subcellular compartments (e.g., nucleus and ribosomes) can accurately predict yeast physiological parameters (e.g., specific growth rate, oxygen uptake rate), and a limited protein set (≥ 23) could be used to capture the variation in resource allocation across seven major subcellular compartments. Furthermore, our comparative analysis between Crabtree-positive and Crabtree-negative species across conditions illustrates that subcellular resource allocation could be shaped by multiple factors and the two species differ markedly in their robustness to environmental perturbations. In summary, the high-quality quantitative proteomic dataset for yeast species offers an unprecedented opportunity for understanding the general principles underlying subcellular resource allocation, laying foundations for precision engineering of cell factories in synthetic biology.
SN - 0027-8424
SN - 1091-6490
ER -