The HIF-1/ BNIP3 pathway mediates mitophagy to inhibit the pyroptosis of fibroblast-like synoviocytes in rheumatoid arthritis

Hong, Zhongyang; Wang, Han; Zhang, Tianjing; Xu, Li; Zhai, Yuanfang; Zhang, Xianzheng; Zhang, Feng; Zhang, Lingling

doi:10.1016/j.intimp.2023.111378

Cited by 7 publications

(2 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with our current results, HIF‐1α has been implicated in the regulation of inflammatory responses and cell death pathways, particularly NLRP3 inflammasome‐associated pyroptosis. 49 , 50 , 51 HIF‐1α appears to regulate the expression of NLRP3, and mitophagy can suppress pyroptosis by blocking the HIF‐1α/NLRP3 pathway under hypoxia. 50 miRNA‐18a inhibits HIF1‐α/NLRP3 signalling to hinder pyroptosis and impair osteogenic differentiation.…”

Section: Discussionmentioning

confidence: 99%

“… 49 , 50 , 51 HIF‐1α appears to regulate the expression of NLRP3, and mitophagy can suppress pyroptosis by blocking the HIF‐1α/NLRP3 pathway under hypoxia. 50 miRNA‐18a inhibits HIF1‐α/NLRP3 signalling to hinder pyroptosis and impair osteogenic differentiation. 51 HIF‐1α‐mediated glycolysis deficiency also alleviates NLRP3‐related inflammation, pyroptosis and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mitochondrial dysfunction induced by HIF‐1α under hypoxia contributes to the development of gastric mucosal lesions

Xiao,

Liu,

Xie

et al. 2024

Clinical & Translational Med

View full text Add to dashboard Cite

IntroductionHypoxia is an important characteristic of gastric mucosal diseases, and hypoxia‐inducible factor‐1α (HIF‐1α) contributes to microenvironment disturbance and metabolic spectrum abnormalities. However, the underlying mechanism of HIF‐1α and its association with mitochondrial dysfunction in gastric mucosal lesions under hypoxia have not been fully clarified.ObjectivesTo evaluate the effects of hypoxia‐induced HIF‐1α on the development of gastric mucosal lesions.MethodsPortal hypertensive gastropathy (PHG) and gastric cancer (GC) were selected as representative diseases of benign and malignant gastric lesions, respectively. Gastric tissues from patients diagnosed with the above diseases were collected. Portal hypertension (PHT)‐induced mouse models in METTL3 mutant or NLRP3‐deficient littermates were established, and nude mouse gastric graft tumour models with relevant inhibitors were generated. The mechanisms underlying hypoxic condition, mitochondrial dysfunction and metabolic alterations in gastric mucosal lesions were further analysed.ResultsHIF‐1α, which can mediate mitochondrial dysfunction via upregulation of METTL3/IGF2BP3‐dependent dynamin‐related protein 1 (Drp1) N6‐methyladenosine modification to increase mitochondrial reactive oxygen species (mtROS) production, was elevated under hypoxic conditions in human and mouse portal hypertensive gastric mucosa and GC tissues. While blocking HIF‐1α with PX‐478, inhibiting Drp1‐dependent mitochondrial fission via mitochondrial division inhibitor 1 (Mdivi‐1) treatment or METTL3 mutation alleviated this process. Furthermore, HIF‐1α influenced energy metabolism by enhancing glycolysis via lactate dehydrogenase A. In addition, HIF‐1α‐induced Drp1‐dependent mitochondrial fission also enhanced glycolysis. Drp1‐dependent mitochondrial fission and enhanced glycolysis were associated with alterations in antioxidant enzyme activity and dysfunction of the mitochondrial electron transport chain, resulting in massive mtROS production, which was needed for activation of NLRP3 inflammasome to aggravate the development of the PHG and GC.ConclusionsUnder hypoxic conditions, HIF‐1α enhances mitochondrial dysfunction via Drp1‐dependent mitochondrial fission and influences the metabolic profile by altering glycolysis to increase mtROS production, which can trigger NLRP3 inflammasome activation and mucosal microenvironment alterations to contribute to the development of benign and malignant gastric mucosal lesions.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mitochondrial dysfunction induced by HIF‐1α under hypoxia contributes to the development of gastric mucosal lesions

Xiao,

Liu,

Xie

et al. 2024

Clinical & Translational Med

View full text Add to dashboard Cite

show abstract

Salidroside ameliorates macrophages lipid accumulation and atherosclerotic plaque by inhibiting Hif-1α-induced pyroptosis

Guo,

Huang,

Bian

et al. 2025

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

IRF1-mediated upregulation of PARP12 promotes cartilage degradation by inhibiting PINK1/Parkin dependent mitophagy through ISG15 attenuating ubiquitylation and SUMOylation of MFN1/2

Deng,

Long,

et al. 2024

Bone Res

View full text Add to dashboard Cite

Osteoarthritis (OA) is an age-related cartilage-degenerating joint disease. Mitochondrial dysfunction has been reported to promote the development of OA. Poly (ADP-ribose) polymerase family member 12 (PARP12) is a key regulator of mitochondrial function, protein translation, and inflammation. However, the role of PARP12 in OA-based cartilage degradation and the underlying mechanisms are relatively unknown. Here, we first demonstrated that PARP12 inhibits mitophagy and promotes OA progression in human OA cartilage and a monosodium iodoacetate-induced rat OA model. Using mass spectrometry and co-immunoprecipitation assay, PARP12 was shown to interact with ISG15, upregulate mitofusin 1 and 2 (MFN1/2) ISGylation, which downregulated MFN1/2 ubiquitination and SUMOylation, thereby inhibiting PINK1/Parkin-dependent chondrocyte mitophagy and promoting cartilage degradation. Moreover, inflammatory cytokine-induced interferon regulatory factor 1 (IRF1) activation was required for the upregulation of PARP12 expression, and it directly bound to the PARP12 promoter to activate transcription. XAV-939 inhibited PARP12 expression and suppressed OA pathogenesis in vitro and in vivo. Clinically, PARP12 can be used to predict the severity of OA; thus, it represents a new target for the study of mitophagy and OA progression. In brief, the IRF1-mediated upregulation of PARP12 promoted cartilage degradation by inhibiting PINK1/Parkin-dependent mitophagy via ISG15-based attenuation of MFN1/2 ubiquitylation and SUMOylation. Our data provide new insights into the molecular mechanisms underlying PARP12-based regulation of mitophagy and can facilitate the development of therapeutic strategies for the treatment of OA.

show abstract

The HIF-1/ BNIP3 pathway mediates mitophagy to inhibit the pyroptosis of fibroblast-like synoviocytes in rheumatoid arthritis

Cited by 7 publications

References 65 publications

Mitochondrial dysfunction induced by HIF‐1α under hypoxia contributes to the development of gastric mucosal lesions

Mitochondrial dysfunction induced by HIF‐1α under hypoxia contributes to the development of gastric mucosal lesions

Salidroside ameliorates macrophages lipid accumulation and atherosclerotic plaque by inhibiting Hif-1α-induced pyroptosis

IRF1-mediated upregulation of PARP12 promotes cartilage degradation by inhibiting PINK1/Parkin dependent mitophagy through ISG15 attenuating ubiquitylation and SUMOylation of MFN1/2

Contact Info

Product

Resources

About