Intraperoxisomal redox balance in mammalian cells: oxidative stress and interorganellar cross-talk

Abstract

Peroxisomes are capable of reactive oxygen species (ROS) generation, but their contribution to cellular redox balance is not well understood. This study demonstrates that peroxisomes and mitochondria functionally interact via ROS signaling, suggesting a potential broader role for the peroxisome in cellular aging and the initiation and progression of age-related diseases.

Molecular Mechanisms and Physiological Significance of Organelle Interactions and Cooperation

“…However, as for mitochondria, this most likely depends on the (patho) physiological state and growth environment of the cell. This idea is in line with the observation that the intraperoxisomal redox state is strongly influenced by various genetic and environmental factors (Ivashchenko et al, 2011). In the following subsections, we further discuss how peroxisomal metabolism of fatty acids, acyl-CoA esters, and plasmalogens may impact on cellular redox state alterations.…”

“…Indeed, as the peroxisomal membrane contains a nonselective pore-forming protein (PXMP2) with an upper molecular size limit of 300-600 Da , these low molecular weight antioxidants can most likely freely diffuse through the peroxisomal membrane. The observations that (i) a peroxisomal variant of roGFP2, a genetically-encoded redox sensor that specifically equilibrates with the GSSG/GSH redox pair, quickly responds to redox changes in the peroxisomal matrix, and (ii) supplementation of vitamin C to the cell culture medium causes an increase in the intraperoxisomal redox state, are in line with this hypothesis (Ivashchenko et al, 2011). However, the precise mechanisms underlying the latter, rather unexpected observation remain to be unraveled.…”

“…Peroxisomes and mitochondria cooperate in cellular lipid metabolism, in particular the breakdown of fatty acids via their organellespecific β-oxidation pathways and can both act as subcellular source, sink or target of ROS Wanders and Waterham, 2006;Ivashchenko et al, 2011;. Although peroxisomes and mitochondria can be observed in close proximity, e.g., in ultrastructural studies in mammalian cells and can also be co-purified at distinct buoyant densities (Hicks and Fahimi, 1977;Islinger et al, 2006), studies on the molecular background of physical interactions and their physiological importance are scarce (Horner et al, 2011(Horner et al, , 2015Van Bergeijk et al, 2015).…”

“…Both organelles are crucial for cellular redox homeostasis . Interestingly, disturbances in peroxisomal lipid and ROS metabolism have an impact on the mitochondrial redox balance (Koepke et al, 2008;Ivashchenko et al, 2011;Walton and Pizzitelli, 2012). It is hypothesized that such peroxisomal disturbances can trigger redox-related signaling events that ultimately result in increased mitochondrial stress and the activation of mitochondrial stress pathways (Titorenko and Terlecky, 2011;.…”

Peroxisomes, oxidative stress, and inflammation

“…A major redox-based interplay exists between peroxisomes and mitochondria, a relationship that warrants additional analysis. Several reports indicate that altering peroxisomal redox balance triggers oxidative stress in mitochondria -resulting in reactive oxygen species production, diminished membrane potential, and compromised organelle function [7,21] . Obviously, the cellular consequences of diminished mitochondrial function are profound.…”