Peroxisomes maintain mitochondrial redox through contact mediated ROS transfer

The formation of reactive oxygen species (ROS) in the mitochondria by the electron transport chain is a necessary and detrimental by-product of oxidative metabolism. Maintenance of mitochondrial redox homeostasis is understood to be a compartmentalized process where mitochondria localized antioxidant systems scavenge mitochondria-derived ROS. However, longstanding evidence that defects in peroxisomes can lead to ROS-mediated damage in the mitochondria challenges this dogma. Here, I describe a direct role for peroxisomes in maintaining mitochondrial redox homeostasis through a mechanism of contact-mediated transfer of ROS. I demonstrate that peroxisomal membrane protein ACBD5 and outer mitochondrial membrane protein PTPIP51 form a previously unidentified peroxisome-mitochondria contact site and show that this contact dynamically increases in response to mitochondrial oxidative stress to maintain mitochondrial redox homeostasis via the transfer of mitochondrial ROS to the peroxisome lumen. My results uncover a new layer of mitochondrial antioxidant defense, elucidating a direct mechanism by which peroxisomes contribute to mitochondrial health and broadening the scope of known membrane contact site functions.