NLRX1/FUNDC1/NIPSNAP1‐2 axis regulates mitophagy and alleviates intestinal ischaemia/reperfusion injury

Abstract

Ischaemic reperfusion (IR) injury is characterized as the damage caused to the tissues due to the return of blood supply (reperfusion) after a brief duration of lack of oxygen (ischaemia). Affecting a wide range of population and organs, they are usually observed as a consequence to conditions such as trauma, shock, strangulation, mesenteric artery thrombosis and intestinal obstruction. 1-4 Ischaemia by itself damages the cells, which is further exacerbated by the restoration of blood flow resulting in increased cell death and release of inflammatory response elements that ultimately leads to multiple organ failure. 5 Of the organs affected by IR injury, the intestine has been described as the most vulnerable to this damage and severe intestinal injury could lead to the need for immediate surgical

Melatonin Improved the Survival of Multi-Territory Perforator Flaps by Promoting Angiogenesis and Inhibiting Apoptosis via the NRF2/FUNDC1 Axis

“…Interestingly, Wang et al ( Wang et al, 2021 ) proposed that FUNDC1 was an integral mitochondrial outer-membrane protein that could increase the expression of VEGF and promote endothelial cell angiogenesis. Similarly, FUNDC1 not only alleviates ischemia–reperfusion injury but also inhibits apoptosis ( Wang et al, 2018 ; Jiang X. et al, 2021 ; Cai et al, 2021 ; Li et al, 2021 ). In our study, we observed that MLT treatment reduced the area of ischemic necrosis of the flap.…”

Bioinformatics and Experimental Analyses Reveal NFIC as an Upstream Transcriptional Regulator for Ischemic Cardiomyopathy

“…Among the top 50 significant DEGs ( Table 1 ), several genes, such as ERBB3 , RCAN1 , and NLRX1 were previously reported to be related with ICM [ 32 , 33 , 34 , 35 , 36 ]. ERRB3 , erb-b2 receptor tyrosine kinase 3, has been reported as a protective factor which inhibits death mechanisms activated by redox stress and supports an involvement of this receptor in the pro-survival responses after MI/R injury [ 32 ].…”

“…Moreover, cardiomyocytes depleted of RCAN1 were more sensitive to simulated MI/R and the calcineurin/Rcan1-signaling cascade could act as a potential therapeutic target through which to benefit from innate circadian changes in cardiac protection without disrupting core circadian oscillations that are essential to cardiovascular, metabolic, and mental health [ 34 ]. NLRX1 , NOD-like receptors family member X1, is significantly downregulated following intestinal MI/R injury [ 35 ], and ablation of the mitochondrial NLRX1 exerts a detrimental effect on acute cardiac infarction induced by a prolonged ischemia-reperfusion episode and activates potential MI/R injury mechanisms contributing to increased MI/R injury, related to elevated energy metabolism and diminished Akt [ 36 ].…”

The Role of Mitophagy in Regulating Cell Death

“…FUNDC1-related mitochondrial dysfunction contributes to various pathophysiological processes, such as heart diseases, intestinal ischemia/reperfusion injury, and metabolic disorders. FUNDC1 is generally considered to be protective in these diseases because FUNDC1-mediated mitophagy can alleviate the damage caused by intracellular stress such as hypoxia and thus benefit overall outcomes [79][80][81]. FUNDC1 is also localized in mitochondrial-associated endoplasmic reticulum membranes (MAMs) and plays a significant role in the communication between the ER and mitochondria in the heart and sustains normal cardiac function [82].…”