{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nFUNDC1 is a mitochondrial outer membrane protein that serves as a receptor for mitophagy, the selective autophagic removal of damaged mitochondria. It interacts directly with LC3 to facilitate mitochondrial clearance under stress conditions such as hypoxia and ischemia/reperfusion injury. In addition, regulatory molecules including specific microRNAs (for example, miR‐137) modulate FUNDC1 expression and activity, thereby altering mitochondrial–endoplasmic reticulum contact sites and overall mitochondrial quality control. This core function is fundamental to the maintenance of cellular bioenergetics and survival in response to cellular stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in mitochondrial clearance, FUNDC1 critically influences cell fate by modulating diverse death pathways such as apoptosis, necroptosis, and PANoptosis. Its activity affects inflammatory signaling by controlling the release of mitochondrial DNA and regulating inflammasome activation, which in turn modulates the production of proinflammatory cytokines like interleukin‑1β. Such regulatory functions have been implicated in conditions ranging from hepatocellular carcinoma and chronic obstructive pulmonary disease to cerebral hemorrhage and hypoxic pulmonary hypertension. Moreover, FUNDC1‐mediated mitophagy is essential for proper differentiation of progenitor cells and for maintaining the balance between mitochondrial fission and fusion in stressed cardiomyocytes, thereby influencing tissue remodeling and repair processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDysregulation of FUNDC1-mediated mitophagy has profound pathological and therapeutic implications. Inadequate FUNDC1 activity contributes to the progression of liver fibrosis, pancreatic β‑cell lipotoxicity, cardiomyocyte dysfunction in cardiorenal syndrome, and neuronal injury following ischemia/reperfusion, as well as to neurodegenerative conditions such as amyotrophic lateral sclerosis. Moreover, enhanced platelet mitophagy driven by elevated FUNDC1 levels has been linked to hyperactivity in diabetes. Interventions that modulate FUNDC1—whether by genetic manipulation, exercise-induced upregulation, or pharmacological inhibition using specific peptide inhibitors—offer promising strategies toward restoring mitochondrial homeostasis and mitigating tissue injury in these diverse pathologies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wen Li, Xingli Zhang, Haixia Zhuang, et al. 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