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. 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. —Stella M. Hurtley [ABSTRACT FROM AUTHOR]