FUNDC1 (FUN14 domain containing 1) is a protein located in the outer mitochondrial membrane and mitochondrial-associated membranes (MAMs), playing a crucial role in regulating mitochondrial quality control through mitophagy, mitochondrial dynamics, and biogenesis. It contains an LC3 interaction region (LIR) motif that binds to LC3, facilitating the selective degradation of damaged mitochondria to maintain cellular health. Under hypoxic conditions, FUNDC1 is phosphorylated by ULK1 and dephosphorylated by PGAM5, enhancing its interaction with LC3 and promoting mitophagy. Additionally, FUNDC1 collaborates with OPA1 to modulate mitochondrial dynamics, and its phosphorylation state affects mitochondrial morphology and the balance between fusion and fission. It is extensively expressed in the heart and has been implicated in various diseases, including metabolic cardiomyopathy, cardiac remodeling, and myocardial ischemia-reperfusion injury.
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