ArticleBMC biology2012
Imbalance of heterologous protein folding and disulfide bond formation rates yields runaway oxidative stress.
Article in BMC biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 102 citations in OpenAlex.
- Integrated stress signaling pathways promote adaptive reprogramming for chondrocyte survival in Metaphyseal Chondrodysplasia Type Schmid.Bone research · 2026Article
- Phenotyping transcription factors-related genotypes in Y. lipolytica across a range of industrially relevant process parameters and chemical stress conditions.Microbial cell factories · 2026Article
- Potential Therapeutic Strategies for Steatosis, Oxidative Stress, Inflammation, and Fibrosis in Liver Disease.International journal of molecular sciences · 2026Review
- Yippee-like protein Moh1 links gene expression to metabolism and selective stress resistance inMicrobial cell (Graz, Austria) · 2026Article
- Enhancing recombinant protein production through Cre-loxP mediated chromosomal rearrangement evolution in Kluyveromyces marxianus.Communications biology · 2025Article
- Impact of Oxygen Availability on the Organelle-Specific Redox Potentials and Stress in Recombinant Protein Producing Komagataella phaffii.Microbial biotechnology · 2025Article
- Characterizing heterologous protein burden in Komagataella phaffii.FEMS yeast research · 2025Article
- Synergistic increase in coproporphyrin III biosynthesis by mitochondrial compartmentalization in engineeredSynthetic and systems biotechnology · 2024Article
- Coupling thermotolerance and high production of recombinant protein by CYR1Communications biology · 2024Article
- Disulfidptosis decoded: a journey through cell death mysteries, regulatory networks, disease paradigms and future directions.Biomarker research · 2024Review
- Genome-wide screen identifies new set of genes for improved heterologous laccase expression in Saccharomyces cerevisiae.Microbial cell factories · 2024Article
- Transcription factors enhancing synthesis of recombinant proteins and resistance to stress in Yarrowia lipolytica.Applied microbiology and biotechnology · 2023Article
- Molecular background of HAC1-driven improvement in the secretion of recombinant protein inBiotechnology reports (Amsterdam, Netherlands) · 2023Article
- Overexpression of genes by stress-responsive promoters increases protein secretion in Saccharomyces cerevisiae.World journal of microbiology & biotechnology · 2023Article
- Taurine alleviates oxidative stress in porcine mammary epithelial cells by stimulating the Nrf2-MAPK signaling pathway.Food science & nutrition · 2023Article
- Comprehensive Analysis of Signal Peptides in Saccharomyces cerevisiae Reveals Features for Efficient Secretion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Secretion of collagenases by Saccharomyces cerevisiae for collagen degradation.Biotechnology for biofuels and bioproducts · 2022Article
- "Fight-flight-or-freeze" - how Yarrowia lipolytica responds to stress at molecular level?Applied microbiology and biotechnology · 2022Review
- Yeast Secretes High Amounts of Human Calreticulin without Cellular Stress.Current issues in molecular biology · 2022Article
- Interaction of Periplasmic Fab Production and Intracellular Redox Balance inACS synthetic biology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe protein secretory pathway must process a wide assortment of native proteins for eukaryotic cells to function. As well, recombinant protein secretion is used extensively to produce many biologics and industrial enzymes. Therefore, secretory pathway dysfunction can be highly detrimental to the cell and can drastically inhibit product titers in biochemical production. Because the secretory pathway is a highly-integrated, multi-organelle system, dysfunction can happen at many levels and dissecting the root cause can be challenging. In this study, we apply a systems biology approach to analyze secretory pathway dysfunctions resulting from heterologous production of a small protein (insulin precursor) or a larger protein (α-amylase).
resultsHAC1-dependent and independent dysfunctions and cellular responses were apparent across multiple datasets. In particular, processes involving (a) degradation of protein/recycling amino acids, (b) overall transcription/translation repression, and (c) oxidative stress were broadly associated with secretory stress.
conclusionsApparent runaway oxidative stress due to radical production observed here and elsewhere can be explained by a futile cycle of disulfide formation and breaking that consumes reduced glutathione and produces reactive oxygen species. The futile cycle is dominating when protein folding rates are low relative to disulfide bond formation rates. While not strictly conclusive with the present data, this insight does provide a molecular interpretation to an, until now, largely empirical understanding of optimizing heterologous protein secretion. This molecular insight has direct implications on engineering a broad range of recombinant proteins for secretion and provides potential hypotheses for the root causes of several secretory-associated diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.