Cytosolic PRDX1 acts as an extramitochondrial sink to set mitochondrial H2O2 levels and enable resilience to chronic mitochondrial oxidative stress
accumulation. PRDX1 deficiency sensitized cells to chronic mitochondrial oxidative stress. A targeted CRISPR screen identified the Rab7 GAP TBC1D5, linking mitophagy to cellular survival under these conditions. Consistently, PRDX1/2-deficient cells exhibited elevated mitophagic flux, indicating mitochondrial quality control as a compensatory response. Our study reveals that cytosolic PRDXs critically impact mitochondrial redox homeostasis and provides a systems-level framework for understanding compartmental redox control and stress adaptation.
Authors
- Elena I. Rugarli (ORCID: https://orcid.org/0000-0002-5782-1067)
- Dietrich Trümbach (ORCID: https://orcid.org/0000-0001-9027-3704)
- Jan Riemer (ORCID: https://orcid.org/0000-0002-7574-8457)
- Armindo Salvador (ORCID: https://orcid.org/0000-0002-4442-4900)
- Lidwina Hasberg
- Silvia von Karstedt (ORCID: https://orcid.org/0000-0002-7816-5919)
- Marcus Conrad (ORCID: https://orcid.org/0000-0003-1140-5612)
- Matteo Veronese
- Sarah Gerlich (ORCID: https://orcid.org/0000-0001-8033-0496)
- Fatma Isil Yapici (ORCID: https://orcid.org/0009-0004-9298-8315)
- Lianne JHC Jacobs
- Giada Di Pietro
- Sebastian Doll
- Jens Hansen
- Pascal Gentzsch
Institutions
- Helmholtz Zentrum München (DE)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- University of Coimbra (PT)
Publication Details
- Journal
- Redox Biology
- Published
- 2026-05-01
- DOI
- https://doi.org/10.1016/j.redox.2026.104195
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Ministerium für Kultur und Wissenschaft des Landes Nordrhein-Westfalen
- Fundação para a Ciência e a Tecnologia