Deficiency of mitophagy receptor FUNDC1 impairs mitochondrial quality and aggravates dietary-induced obesity and metabolic syndrome

Wu, Hao; Wang, You; Li, Wenhui; Chen, Hui; Du, Lei; Liu, Dong; Wang, Xiaohui; Xu, Tao; Liu, Lei; Chen, Quan

doi:10.1080/15548627.2019.1596482

Cited by 155 publications

(126 citation statements)

References 78 publications

(85 reference statements)

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“…The host gene of circFUNDC1-FUNDC1 has been verified to play an imperative role in mitophagy. Ablation of the mitophagy receptor FUNDC1 leads to impaired mitophagy, which might partially account for deformed mitochondria and pronounced oxidative stress [17]. Though the precise contribution of FUNDC1 to basal or stimulated (by stress of stroke) mitophagy activity in peripheral blood cells remains undetermined, we hypothesize that mitophagy might be an important aspect of worsening outcomes in stroke patients, especially in peripheral neutrophils that are closely associated with peripheral immune system.…”

Section: Discussionmentioning

confidence: 93%

Circular RNA FUNDC1 improves prediction of stroke associated infection in acute ischemic stroke patients with high risk

Zuo

Cai

et al. 2020

Bioscience Reports

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Identifying those patients who were at high risk of stroke associated infection (SAI) for preventive antibiotic therapy was imperative for patients’ benefits, thus improving prediction of SAI was critical for all acute ischemic stroke (AIS) patients. Circular RNA FUNDC1 (circFUNDC1) has been reported to be the diagnosis and prognosis biomarker of AIS. Therefore, the present study aimed to figure out whether circFUNDC1 could be the potential predictor of SAI that could help to guide preventive treatment. In total, 68 patients were included in the study, 26 of which had infection and 42 without. Copy number of circFUNDC1 in plasma were quantified by quantitative real-time polymerase chain reaction (qPCR). Platelet spike-in experiment and correlation analysis were conducted to explore possible origins of circFUNDC1 in plasma. A significantly elevated level of circFUNDC1 was found in SAI patients compared with not infected AIS patients (P=0.0258). Receiver operating characteristic (ROC) curves demonstrated the prediction significance of circFUNDC1, with the area under the curve (AUC) at 0.6612 and sensitivity, specificity at 69.23%, 61.90% respectively in predicting SAI. Then, when adding circFUNDC1 in the risk model, the AUC increased from 0.7971 in model A to 0.8038 in model B. Additionally, positive correlation was observed between circFUNDC1 level and neutrophils counts. WBC and neutrophil ratios were significantly elevated in SAI patients compared with non-SAI patients. Therefore, circFUNDC1 could be used to construct a risk model for the prediction of SAI that is beneficial for AIS patients’ preventive treatment.

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Section: Discussionmentioning

confidence: 93%

Circular RNA FUNDC1 improves prediction of stroke associated infection in acute ischemic stroke patients with high risk

Zuo

Cai

et al. 2020

Bioscience Reports

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“…FUNDC1 interacts with molecules like LC3B, which is found on the mitochondria-associated membrane of the endoplasmic reticulum, to maintain good mitochondrial quality by forming mitophagosomes (4). FUNDC1related mitochondrial dysfunction contributes to various pathophysiological processes, such as heart diseases, metabolic disorders, and cancers (6)(7)(8)(9). In cardiovascular and metabolic diseases, FUNDC1 is generally considered to be protective because FUNDC1-mediated mitophagy can alleviate damage caused by intracellular stress such as hypoxia and thus benefit overall outcomes (9,10).…”

Section: Introductionmentioning

confidence: 99%

Prognostic and Immunological Role of FUN14 Domain Containing 1 in Pan-Cancer: Friend or Foe?

et al. 2020

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Background: FUN14 domain containing 1 (FUNDC1) plays a pivotal role in mitochondrial autophagy (mitophagy), which is closely associated with human immunity. However, the role of FUNDC1 in cancers remains unclear. This study aimed to visualize the prognostic landscape of FUNDC1 in pan-cancer and investigate the relationship between FUNDC1 expression and immune infiltration. Methods: In this study, we explored the expression pattern and prognostic value of FUNDC1 in pan-cancer across multiple databases, including ONCOMINE, PrognoScan, GEPIA, and Kaplan-Meier Plotter. Then, using the GEPIA and TIMER databases, we investigated the correlations between FUNDC1 expression and immune infiltration in cancers, especially liver hepatocellular carcinoma (LIHC), and lung squamous cell carcinoma (LUSC). Results: In general, compared with that in normal tissue, tumor tissue had a higher expression level of FUNDC1. Although FUNDC1 showed a protective effect on pan-cancer, a high expression level of FUNDC1 was detrimental to the survival of LIHC patients. Although different from what was found for LUSC, for LIHC, there were significant positive correlations between FUNDC1 expression and immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, and dendritic cells. Furthermore, markers of infiltrating immune cells, such as tumor-associated-macrophages (TAMs), exhibited different FUNDC1-related immune infiltration patterns. Conclusion: The mitophagy regulator FUNDC1 can serve as a prognostic biomarker in pan-cancer and is correlated with immune infiltrates.

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“…Furthermore, mitophagy is thought to mediate the protective effect of ischemic preconditioning in kidneys by targeting a series of biological events, including damaged mitochondrial clearance, mitophagosome formation, and mitochondrial depolarization [41]. In addition, crucial roles for mitophagy in affording neuroprotection against IR cerebral injury and alleviating metabolic dysfunction have also been reported [20,[42][43][44]. Under tumor-related hypoxic conditions, the activation of mitophagy is involved in assisting tumor cell survival and promoting cancer, while BNIP3-or BNIP3L-mediated mitophagy may act as a suppressor of tumorigenesis and metastasis in breast cancer or xenograft conditions [45][46][47].…”

Section: Discussionmentioning

confidence: 99%

Locally Activated Mitophagy Contributes to a 'Built-In' Protection Against Early Burn-Wound Progression in Rats Following a Regulation of HIF-1α

et al. 2020

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Background: Deep burn wounds undergo a dynamic progression in the initial or periburn area after insults. The zone of stasis has a higher risk of deterioration and is considered a salvageable target for burn-wound progression. Few studies have explored the role of mitochondrial damage in this process and potential "built-in" self-defense within the human body. Methods: A classic "comb" scald rat model was established in this study. Histological and blood-ow observation were processed based on hematoxylin-eosin staining and laser analysis. Oxidative and apoptotic status were analyzed by commercial kits. Transmission electron microscope, immuno uorescence staining, and western blot were applied to detect the mitophagy happened in the zone of stasis and potential regulators. Adenovirus-based gene-silence contributed to determine the role of HIF-1 as a regulatory mediator. Results: We found that burn insults caused typical ischemia and histological deterioration in the zone of stasis, in parallel with increases in oxidative stress and apoptosis. Mitochondrial damage was also involved in the aforementioned changes. Furthermore, we detected typical mitophagy in burn wounds, which was contradictory to the burn-wound conversion. HIF-1 expression was closely related to the level of mitophagy, while BNIP3 and PARKIN are involved downstream. Conclusion: We demonstrate that burn-induced mitochondrial impairment contributes to the mobilization of injurious mechanisms in the zone of stasis and that mitophagy provides a more bene cial way to protect against burn-wound progression via the elimination of damaged mitochondria. Our ndings offer insights into mitochondrial quality control in burn-wound progression and suggest the novel concept that HIF-1 may be a potential therapeutic target due to its possible regulatory effects upstream of BNIP3-or PARKIN-mediated mitophagy. Background Deep thermal burns can cause irreversible tissue damage to the integument that can further progress over 3 days[1]. Dynamic conversion, including expansion and deepening, can be observed in the peripheral zones of initial wounds of partial thickness or full thickness burns from 48 h to 72 h; this is de ned as burn wound progression[1-3]. Jackson described three concentric zones (coagulation, stasis and hyperemia from the center to the outer region) to explain the histopathological changes that occur in early burn wounds[4]. The intermediate zone, which undergoes stasis characterized by edema and slow blood ow, progresses to irrecoverable necrosis without appropriate interventions, and the zone of stasis is also considered salvageable and provides an opportunity to prevent cutaneous wound conversion after burn injury[1,2,5]. Efforts to attenuate the early deterioration of initial burn wounds are of great importance. The burn-induced ischemic status in the zone of stasis is attributed to multiple pathophysiological mechanisms, such as edema, vasoconstriction and hypercoagulability[2,5]. A number of studies have

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Deficiency of mitophagy receptor FUNDC1 impairs mitochondrial quality and aggravates dietary-induced obesity and metabolic syndrome

Cited by 155 publications

References 78 publications

Circular RNA FUNDC1 improves prediction of stroke associated infection in acute ischemic stroke patients with high risk

Circular RNA FUNDC1 improves prediction of stroke associated infection in acute ischemic stroke patients with high risk

Prognostic and Immunological Role of FUN14 Domain Containing 1 in Pan-Cancer: Friend or Foe?

Locally Activated Mitophagy Contributes to a 'Built-In' Protection Against Early Burn-Wound Progression in Rats Following a Regulation of HIF-1α

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