Redox interplay between mitochondria and peroxisomes

Abstract

Reduction-oxidation or “redox” reactions are an integral part of a broad range of cellular processes such as gene expression, energy metabolism, protein import and folding, and autophagy. As many of these processes are intimately linked with cell fate decisions, transient or chronic changes in cellular redox equilibrium are likely to contribute to the initiation and progression of a plethora of human diseases. Since a long time, it is known that mitochondria are major players in redox regulation and signaling. More recently, it has become clear that also peroxisomes have the capacity to impact redox-linked physiological processes. To serve this function, peroxisomes cooperate with other organelles, including mitochondria. This review provides a comprehensive picture of what is currently known about the redox interplay between mitochondria and peroxisomes in mammals. We first outline the pro- and antioxidant systems of both organelles and how they may function as redox signaling nodes. Next, we critically review and discuss emerging evidence that peroxisomes and mitochondria share an intricate redox-sensitive relationship and cooperate in cell fate decisions. Key issues include possible physiological roles, messengers, and mechanisms. We also provide examples of how data mining of publicly-available datasets from “omics” technologies can be a powerful means to gain additional insights into potential redox signaling pathways between peroxisomes and mitochondria. Finally, we highlight the need for more studies that seek to clarify the mechanisms of how mitochondria may act as dynamic receivers, integrators, and transmitters of peroxisome-derived mediators of oxidative stress. The outcome of such studies may open up exciting new avenues for the community of researchers working on cellular responses to organelle-derived oxidative stress, a research field in which the role of peroxisomes is currently highly underestimated and an issue of discussion.

Ascorbate peroxidase proximity labeling coupled with biochemical fractionation identifies promoters of endoplasmic reticulum–mitochondrial contacts

“…For example, ER-mitochondrial contacts have been most extensively studied and linked to Ca 2ϩ and lipid exchange, intracellular trafficking of ER and mitochondria, ER stress response, autophagy, mitochondrial biogenesis, and inflammasome formation (5-7, 10, 34, 68 -71). Peroxisomes and mitochondria functionally and physically interact to maintain lipid homeostasis through ␤-oxidation of fatty acids and scavenging reactive oxygen species (72,73). Mitochondria are also known to form stable contacts with Golgi and the nuclear envelope (74,75).…”

Toxicological Risk Assessment of Emerging Nanomaterials: Cytotoxicity, Cellular Uptake, Effects on Biogenesis and Cell Organelle Activity, Acute Toxicity and Biodistribution of Oxide Nanoparticles

“…Peroxisomal dysfunctions are associated with important brain diseases [54]. To exert its activities, the peroxisome must interact both functionally and physically with other cell organelles, mainly mitochondria and endoplasmic reticulum [59,60]. It seems therefore important to precise the effects of nanoparticles on peroxisome.…”

Mitochatting – If only we could be a fly on the cell wall

“…Hence, under conditions of excess ROS in one organelle, the cell may shuttle the "overflow" ROS for breakdown in the other. Indeed, in mammalian cells, deficiencies in peroxisomal ROS metabolism impact the mitochondrial redox balance and lead to mitochondrial fragmentation and cell death [113]. In addition, excess oxygen radical production inside peroxisomes causes cellular lipid peroxidation, and triggers a complex network of signaling events eventually resulting in increased mitochondrial H 2 O 2 production [115].…”

“…Reactive oxygen species (ROS): Both mitochondria and peroxisomes are involved in maintaining the cellular redox balance and homeostasis [113]. A reducing environment is maintained in the cytosol, mitochondrial matrix and peroxisomes, in order to facilitate protein folding and activity [114].…”