ROS transfer at peroxisome-mitochondria contact regulates mitochondrial redox

Maintenance of mitochondrial redox homeostasis is of fundamental importance to cellular health. Mitochondria harbor a host of intrinsic antioxidant defenses, but the contribution of extrinsic, nonmitochondrial antioxidant mechanisms is less well understood. We found a direct role for peroxisomes in maintaining mitochondrial redox homeostasis through contact-mediated reactive oxygen species (ROS) transfer. We found that ACBD5 and PTPIP51 form a contact between peroxisomes and mitochondria. The percentage of these contacts increased during mitochondrial oxidative stress and helped to maintain mitochondrial health through the transfer of mitochondrial ROS to the peroxisome lumen. Our findings reveal a multiorganelle layer of mitochondrial antioxidant defense—suggesting a direct mechanism by which peroxisomes contribute to mitochondrial health—and broaden the scope of known membrane contact site functions.

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References

Details

Published: Jul 10, 2025
Vol/Issue: 389(6756)
Pages: 157-162

Authors

L

Laura F. DiGiovanni

Cell and Systems Biology Program, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Canada.; Department of Biochemistry, University of Toronto, Toronto, Canada.

P

Prabhsimran K. Khroud

Cell and Systems Biology Program, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Canada.; Department of Biochemistry, University of Toronto, Toronto, Canada.

R

Ruth E. Carmichael

Biosciences, University of Exeter, Exeter, UK.

T

Tina A. Schrader

Biosciences, University of Exeter, Exeter, UK.

S

Shivneet K. Gill

Department of Biochemistry, University of Toronto, Toronto, Canada.; Molecular Medicine Program, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Canada.

K

Kyla Germain

Cell and Systems Biology Program, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Canada.; Department of Biochemistry, University of Toronto, Toronto, Canada.

R

Robert Y. Jomphe

Cell and Systems Biology Program, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Canada.; Department of Biochemistry, University of Toronto, Toronto, Canada.

C

Christoph Wiesinger

Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Vienna, Austria.

M

Maxime Boutry

Cell and Systems Biology Program, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Canada.

M

Maki Kamoshita

Biosciences, University of Exeter, Exeter, UK.; Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.

D

Daniel Snider

Cell and Systems Biology Program, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Canada.

G

Garret Stubbings

Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Canada.

R

Rong Hua

Cell and Systems Biology Program, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Canada.

N

Noel Garber

Cell and Systems Biology Program, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Canada.; Department of Biochemistry, University of Toronto, Toronto, Canada.

C

Christian Hacker

Biosciences, University of Exeter, Exeter, UK.

A

Andrew D. Rutenberg

Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Canada.

R

Roman A. Melnyk

Department of Biochemistry, University of Toronto, Toronto, Canada.; Molecular Medicine Program, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Canada.

J

Johannes Berger

Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Vienna, Austria.

M

Michael Schrader

Biosciences, University of Exeter, Exeter, UK.

B

Brian Raught

Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Canada.

P

Peter K. Kim

Cell and Systems Biology Program, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Canada.; Department of Biochemistry, University of Toronto, Toronto, Canada.; College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.

Cite This Article

Laura F. DiGiovanni, Prabhsimran K. Khroud, Ruth E. Carmichael, et al. (2025). ROS transfer at peroxisome-mitochondria contact regulates mitochondrial redox. Science, 389(6756), 157-162. https://doi.org/10.1126/science.adn2804

ROS transfer at peroxisome-mitochondria contact regulates mitochondrial redox

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