ROS transfer at peroxisome-mitochondria contact regulates mitochondrial redox, 2025, DiGiovanni et al.

SNT Gatchaman

Senior Member (Voting Rights)
Staff member
ROS transfer at peroxisome-mitochondria contact regulates mitochondrial redox
Laura F. DiGiovanni; Prabhsimran K. Khroud; Ruth E. Carmichael; Tina A. Schrader; Shivneet K. Gill; Kyla Germain; Robert Y. Jomphe; Christoph Wiesinger; Maxime Boutry; Maki Kamoshita; Daniel Snider; Garret Stubbings; Rong Hua; Noel Garber; Christian Hacker; Andrew D. Rutenberg; Roman A. Melnyk; Johannes Berger; Michael Schrader; Brian Raught; Peter K. Kim

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.

EDITOR’S SUMMARY
Mitochondria generate reactive oxygen species (ROS) molecules that can cause oxidative damage if not properly controlled. Mitochondria have been thought to manage their own ROS using built-in antioxidant systems. However, defects in antioxidant-rich organelles called peroxisomes lead to mitochondrial damage. DiGiovanni et al. found a direct role for peroxisomes in managing mitochondrial ROS (see the Perspective by Fransen). Membrane contacts between peroxisomes and mitochondria allow mitochondrial ROS to transfer directly to peroxisomes for processing. This role of peroxisomes as sinks for ROS provides a way for cells to defend themselves against oxidative damage.

Link | PDF | Science [Paywall]
 
Commentary: Organelles share the load

Eukaryotic cells contain organelles that carry out specialized functions essential for organismal health. In mammals, mitochondria primarily generate energy, whereas peroxisomes—named for their role in metabolizing the reactive oxygen species (ROS) hydrogen peroxide (H2O2)—help maintain redox balance. Both organelles also contribute to lipid metabolism and intracellular signaling through distinct yet complementary mechanisms . Their functions and stress responses depend on sustained interorganellar communication, which typically occurs at membrane contact sites (MCSs), regions where organelle membranes are closely apposed and stabilized by molecular tethers. On page 157 of this issue, DiGiovanni et al. (5) report the discov ery of a mammalian peroxisome-mitochondria tethering complex that dynamically responds to mitochondrial oxidative stress—an imbalance in which ROS production exceeds antioxidant defenses—and enables the transfer of ROS from mitochondria to peroxisomes. These findings deepen understanding of the role of MCSs in cell biology and ROS regulation.
 
but the contribution of extrinsic, nonmitochondrial antioxidant mechanisms is less well understood.
Nutraceutical marketers won't like that. "Our amazing antioxidants magically transport themselves to the offending ROS molecules to reduce aging, make you richer and more beautiful, etc."
 
Back
Top Bottom