Ask about this productRelated genes to: FUNDC1 Blocking Peptide
- Gene:
- FUNDC1 NIH gene
- Name:
- FUN14 domain containing 1
- Previous symbol:
- -
- Synonyms:
- MGC51029
- Chromosome:
- Xp11.3
- Locus Type:
- gene with protein product
- Date approved:
- 2004-03-16
- Date modifiied:
- 2019-02-01
Related products to: FUNDC1 Blocking Peptide
Related articles to: FUNDC1 Blocking Peptide
- Mitophagy, a selective autophagic process crucial for mitochondrial quality control, plays a context-dependent dual role in hepatocellular carcinoma (HCC), functioning as both a tumor suppressor and a promoter of malignancy. This review provides a comprehensive analysis of the mechanistic landscape and therapeutic implications of mitophagy in HCC. We detail how mitophagy influences hepatocarcinogenesis, tumor progression, metabolic reprogramming, and the maintenance of liver cancer stem cells (LCSCs). Central to its function are two primary pathways: the ubiquitin-dependent PINK1/Parkin axis and receptor-mediated pathways such as FUNDC1 and BNIP3/NIX, each demonstrating scenario-specific outcomes that contribute to the complexity of HCC biology. A major focus is placed on mitophagy's significant role in fostering resistance to various therapies, including tyrosine kinase inhibitors (TKIs), chemotherapy, and radiotherapy, thereby presenting a formidable clinical challenge. In response, we critically evaluate emerging therapeutic strategies that target mitophagy. These approaches are strategically bifurcated: one aimed at inhibiting pro-survival mitophagy to sensitize tumors to cell death, and another designed to induce excessive, lethal mitophagy for direct cancer cell eradication. We further explore innovative frontiers that integrate mitophagy modulation with immunotherapy, metabolic intervention, and tumor microenvironment (TME) remodeling. This review underscores mitophagy as a pivotal yet complex therapeutic node in HCC. It concludes that a nuanced, context-dependent understanding of mitophagy's dual functions is essential for developing precise and effective treatment strategies to combat this aggressive cancer. - Source: PubMed
Publication date: 2026/02/26
Guo QinyuWang HangZhu LeiDeng HongsongJiang Zhongyong - Combination therapies are critical for enhancing and prolonging the efficacy of EGFR inhibitors. Here, we uncover FUNDC1-dependent mitophagy as a key protective mechanism in EGFR-mutant non-small cell lung cancer (NSCLC). We discover that nitidine, a bioactive component of the traditional Xihuang Pill formulation, synergises with the EGFR inhibitor osimertinib. Mechanistically, nitidine and osimertinib synergistically disrupt FUNDC1-mediated mitophagy, leading to mitochondrial dysfunction and accumulation of reactive oxygen species in EGFR-mutant NSCLC. We further show that both osimertinib and nitidine decrease HIF-1α protein levels, thereby downregulating FUNDC1 expression. Nitidine-induced downregulation of HIF-1α and FUNDC1 depends on the mitochondrial transporter ABCB6. Notably, acquired resistance to osimertinib exhibits adaptive downregulation of FUNDC1, rendering resistant EGFR-mutant NSCLC cells more sensitive to nitidine. Collectively, these findings position nitidine as a promising therapeutic strategy to enhance the efficacy of EGFR inhibitors and overcome osimertinib resistance in EGFR-mutant NSCLC. - Source: PubMed
Xu FanWang XiaoshanLi MinLi YiLi XiaojuanYan QingqingKong FanmingHuang QihongCao XinXue Ying - Defining molecular pathways driving β-cell failure in type 2 diabetes (T2D) is challenging given donor heterogeneity. We developed an interpretable machine learning framework coupling sparse rule-based classification, pathway constrained modeling, and mitochondrial fitness stratification, applied to single-cell RNAseq from 52 human islet donors. A 50-gene classifier predicted T2D at single-cell resolution, outperforming ensemble models, with donor-level scores correlating with HbA1c. We identified a resilient non-diabetic (ND) β-cell subtype with preserved β-cell identity, while T2D β-cell subtypes showed cellular stress and suppressed oxidative phosphorylation. Mitophagy emerged as the dominant cellular pathway, with PINK1, BNIP3, and FUNDC1 as predictors. At the donor level, PINK1 expression decreased with T2D score and correlated with sex‑specific mitophagy patterns. We developed a mitochondrial fitness index (MFI, R² = 0.934) integrating mitophagy, proteostasis, biogenesis, and respiration, identifying PINK1, SQSTM1, PRKN, and BNIP3 as top T2D contributors. Interpretable machine learning revealed mitophagy as central to β-cell metabolic fitness. - Source: PubMed
Publication date: 2026/05/18
Qadir Mirza Muhammad FahdDana CharlesPittigher MadeleineMauvais-Jarvis PaulHaque NazmulDos Santos TheodoreE MacDonald PatrickJ Gaulton KyleMauvais-Jarvis Franck - Sepsis is a dysregulated host immune response to pathogen infection, characterized by an initial acute hyperinflammatory response followed by persistent immunosuppression. The immunosuppressive phase of sepsis is characterized by a marked impairment in the capacity of monocytes/macrophages to produce pro-inflammatory cytokines, a dysfunction linked to severe mitochondrial metabolic defects. Mitophagy is a crucial cellular process that regulates macrophage inflammation by maintaining mitochondrial homeostasis. FUN14domain- containing 1 (FUNDC1) is a known mitophagy receptor, but its role in macrophages during sepsis-induced immunosuppression remains unclear. In this study, we found that FUNDC1-mediated mitophagy is suppressed in immunosuppressive macrophages. Furthermore, both FUNDC1 knockdown and a cell-penetrating FUNDC1-inhibitory peptide P (CPP-P) further suppressed pro-inflammatory cytokines production in immunosuppressive macrophages. Mechanistic studies demonstrated that suppressing FUNDC1-dependent mitophagy exacerbates metabolic dysfunction of immunosuppressive macrophages. Additionally, CPP-P-treated mice exhibit reduced pro-inflammatory cytokines release and impaired bacterial clearance, resulting in exacerbated lung tissue damage and elevated mortality during the immunosuppressive phase of sepsis. Collectively, our study demonstrates that suppression of FUNDC1-mediated mitophagy in macrophages contributes to the immunocompromised state in sepsis and reveals potential therapeutic targets. - Source: PubMed
Publication date: 2026/05/17
Cai MingjingWang YaweiZhong YujieWang HuanyuLi QiuliDai WenjingXie YujiaoTang MingxinShen LinChen WenyingYang LingWang YuShi ChunmengMa Lijie - Cerebral ischemia-reperfusion injury (CIRI) refers to a cascade of pathological events initiated by the restoration of blood flow to ischemic brain regions in patients with cerebral infarction. This process leads to mitochondrial dysfunction through mechanisms including oxidative stress, calcium overload, inflammation, and impaired energy metabolism. FUN14 domain containing 1 (FUNDC1), a key receptor protein involved in mitochondrial autophagy, plays a crucial protective role in CIRI by regulating mitophagy and maintaining mitochondrial quality control. This function is governed by the dynamic phosphorylation and dephosphorylation of FUNDC1, which finely modulate the activation and inhibition of mitophagy, thereby attenuating mitochondrial dysfunction. Moreover, FUNDC1 is implicated in mitochondrial fission, the clearance of unfolded proteins, mitochondrial iron metabolism, and inter-organelle communication, collectively contributing to the regulation of cellular metabolism and immune responses. Therefore, targeting FUNDC1-mediated mitophagy to restore mitochondrial quality control and reduce mitochondrial dysfunction represents a promising therapeutic strategy for CIRI. This review summarizes the role of FUNDC1 in mitochondrial dynamic homeostasis, inter-organelle communication, and CIRI, highlighting its potential as a therapeutic target. - Source: PubMed
Publication date: 2026/05/15
Zou Xin-YiCai Luo-YangZhang JinYuan YingSong JieHu Zhao-DuanPeng RuiRuan Xiao-FengZhang Xiao-Ming