Endoplasmic Reticulum Redoxome: Protein Folding and Beyond.
Percillia V S Oliveira1, Tiphany C De Bessa1, Francisco R M Laurindo1
1Laboratorio de Biologia Vascular (LVascBio), LIM-64, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, São Paulo CEP 05403-000, Brazil.
Biochemistry
|December 12, 2025
Summary
The endoplasmic reticulum (ER) maintains a unique oxidizing environment crucial for protein folding and redox homeostasis. This ER redoxome extends beyond the cell, influencing intercellular communication and cellular health.
Area of Science:
- Cellular Biology
- Biochemistry
- Redox Biology
Background:
- The endoplasmic reticulum (ER) is vital for protein processing, relying on a specific redox environment.
- This environment supports disulfide bond formation and protein folding through various oxidoreductases.
- ER redox state is linked to cellular homeostasis and stress responses.
Purpose of the Study:
- To provide a comprehensive overview of the ER redoxome.
- To highlight the ER's role in intra- and intercellular redox communication.
- To introduce the concept of the ER-dependent outreach redoxome (ERDOR).
Main Methods:
- Literature review and synthesis of existing research on ER redox biology.
- Analysis of the interplay between ER redox state, calcium fluxes, and organelle contacts.
- Examination of ER oxidoreductase translocation and extracellular redox signaling.
Main Results:
- The ER maintains an oxidizing environment essential for disulfide bond formation and protein processing.
- Interacting pathways involving protein disulfide isomerases (PDIs) and Ero1α regulate ER redox homeostasis.
- The ER redoxome extends to other organelles and the extracellular space (ERDOR) via oxidoreductase translocation.
- ER-membrane contacts and calcium fluxes significantly influence ER redox dynamics.
- Extracellular ER oxidoreductases regulate molecular targets and form peri/epicellular redox networks.
Conclusions:
- The ER redoxome is a critical emerging area for understanding redox proteostasis.
- ER redox mechanisms are fundamental to both intracellular and intercellular redox communication.
- The ER-dependent outreach redoxome (ERDOR) extends ER's redox influence beyond the cell.
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