Deficiency of β-carotene oxygenase 2 induces mitochondrial fragmentation and activates the STING-IRF3 pathway in the mouse hypothalamus

Activation of the STING‐IRF3 pathway involved in psoriasis with diabetes mellitus

“…22,31,32 Recently, it was reported that the STING-IRF3 pathway can be activated by ER stress 19 and mitochondrial damage. 20,27,33 Additionally, IMQ has been reported to alter intracellular redox states. The inhibition of mitochondrial complex I by IMQ can induce the production of a large number of reactive oxygen species (ROS), damage mitochondria and disrupt mitochondrial balance.…”

“…In addition, there is growing evidence indicating that mtDNA escaping from stressed mitochondria can activate inflammasomes and participate in the cGAS-STING pathway to induce interferon production. 27,35 Previous studies have shown that 36 in keratinocytes, oxidative stress in a high-glucose environment can cause ROS overload which triggers mitochondrial dysfunction, accelerate TFAM depletion, and mtDNA fragmentation. 20 The abnormally packaged mtDNA escapes from the mitochondria to the cytoplasm and is recognized by the DNA sensor cGAS which then activates the STING-IRF3 pathway, thus regulating immunity and metabolism.…”

“…Previous studies have suggested that mitochondrial damage activates STING. 20,27 To understand the possible role of the STING-IRF3 pathway involved in the development of psoriasis with T2DM, we examined oxidative stress levels and expression levels of mitochondria-related proteins and genes in the mouse model of psoriasis with diabetes. Malondialdehyde was used as a biomarker for oxidative stress levels.…”

Astaxanthin as a Novel Mitochondrial Regulator: A New Aspect of Carotenoids, beyond Antioxidants

“…It has been reported that mice with whole-body knockout of BCDO2 function developed metabolic dysfunction derived from the peripheral and hypothalamus, even when fed a diet thought to be free of carotenoids. Importantly, failure of gene expression related to the antioxidant response, such as Nrf2, was observed frequently in the knockout mice used in these studies [ 104 , 105 , 106 ]. In conclusion, although the level of influence of AX on this pathway is not known, it is suggested that carotenoids may activate Nrf-2 in a different way to the commonly known Nrf2/Keap1 pathway ( Figure 3 .).…”

“…In relation to AX, the effect of BCDO2-generated AX metabolites should be considered in the future, because it has only been studied in toxicological aspects, such as CYP induction in rats [ 125 ]. Perhaps independently of these features, BCDO2 itself probably functions as an anti-inflammatory factor through the modulation of several signaling pathways and gene expression [ 103 , 104 , 105 , 106 , 236 , 237 ].…”