Peroxisomes in Immune Response and Inflammation

Abstract

The immune response is essential to protect organisms from infection and an altered self. An organism’s overall metabolic status is now recognized as an important and long-overlooked mediator of immunity and has spurred new explorations of immune-related metabolic abnormalities. Peroxisomes are essential metabolic organelles with a central role in the synthesis and turnover of complex lipids and reactive species. Peroxisomes have recently been identified as pivotal regulators of immune functions and inflammation in the development and during infection, defining a new branch of immunometabolism. This review summarizes the current evidence that has helped to identify peroxisomes as central regulators of immunity and highlights the peroxisomal proteins and metabolites that have acquired relevance in human pathologies for their link to the development of inflammation, neuropathies, aging and cancer. This review then describes how peroxisomes govern immune signaling strategies such as phagocytosis and cytokine production and their relevance in fighting bacterial and viral infections. The mechanisms by which peroxisomes either control the activation of the immune response or trigger cellular metabolic changes that activate and resolve immune responses are also described.

HSD17B4, ACAA1, and PXMP4 in Peroxisome Pathway Are Down-Regulated and Have Clinical Significance in Non-small Cell Lung Cancer

“…The genes were applied to enrichment analysis and they were significant enriched in 11 terms (Figure 8B). Interestingly, except peroxisome, several immune-related processes including phagocytosis, regulation of adaptive immune response, regulation of lymphocyte mediated immunity, and ECM affiliated were enriched, consistent with the associations of peroxisomes with immune response and inflammation reported in previous studies (Vijayan et al, 2017;Di Cara et al, 2019), indicating the implication of HSD17B4, ACAA1, and PXMP4 in these processes.…”

HMGB1 Translocation in Neurons after Ischemic Insult: Subcellular Localization in Mitochondria and Peroxisomes

“…The presence of HMGB1 in the peroxisomes strongly suggested that HMGB1 played another role in the functional regulation of cellular oxidative stress. Based on the specific localization of catalase, an H 2 O 2 -degrading enzyme, and other redox-related enzymes in peroxisomes, it has been speculated that peroxisomes are involved in the regulation of the redox state and a related intracellular signaling pathway [22,23]. Three cysteine residues on HMGB1 were reported to be sensitive to oxidative stress and to respectively form three kinds of molecular species: an all-thiol form, a disulfide form, and a sulfoxide form.…”

“…Further studies will be needed to determine the molecular species of HMGB1 in the ischemic brain. In addition to the redox regulation, it has recently been suggested that peroxisomes function as pivotal regulators of immune functions and inflammation through immunometabolism [22]. It is worthy of mention that two HMGB1-localizing subcellular organelles, i.e., mitochondria and peroxisomes, might have a special interaction spatially and functionally [22,24].…”

“…In addition to the redox regulation, it has recently been suggested that peroxisomes function as pivotal regulators of immune functions and inflammation through immunometabolism [22]. It is worthy of mention that two HMGB1-localizing subcellular organelles, i.e., mitochondria and peroxisomes, might have a special interaction spatially and functionally [22,24]. Although a little is known about the regulatory role of HMGB1 in cell metabolism, the translocation of HMGB1 attached to peroxisomes during the ischemic responses in neurons may be related to the cellular metabolism.…”

Molecular Chaperones: Molecular Assembly Line Brings Metabolism and Immunity in Shape

“…Peroxisomes are closely connected to the communication between mitochondria and ER through lipid and ROS metabolic pathways, essential metabolites and signals in cellular immune responses [ 175 , 176 , 177 ]. Polyunsaturated fatty acids (PUFAs) generated by peroxisomes are essential for the synthesis of pro-resolving mediators (e.g., resolvins) to the resolution of inflammation [ 178 , 179 ]. Peroxisomes can regulate cellular cholesterol homeostasis.…”