FUN14 domain-containing protein 1 (FUNDC1)

FUN14 domain-containing protein 1 (FUNDC1) is a highly conserved outer mitochondrial membrane protein that acts as a receptor for mitophagy, mediating the selective autophagic degradation of mitochondria. FUNDC1’s key molecular feature is its LC3-interaction region (LIR), which binds to autophagosomal membrane protein LC3 (MAP1LC3 family), initiating the mitophagy process, especially under hypoxic stress. Modifications at specific phosphorylation and ubiquitination sites on FUNDC1 modulate its activity, integrating cellular stress signals. FUNDC1 is implicated in the maintenance of mitochondrial morphology, dynamics, and proper function, by controlling mitochondrial fission/fusion and interactions at mitochondria-associated ER membranes (MAMs)[7][2]. It is especially expressed in the heart and is considered a potential therapeutic target and biomarker for diseases where mitochondrial dysfunction is a central feature, including cardiovascular diseases and cancers. While no approved drugs selectively target FUNDC1 yet, it is under active investigation for its fundamental role in cell fate and health[3][5][2].

Other names

FUNDC1FUN14 domain containing 1[9]

Modulation of FUNDC1 phosphorylation or ubiquitination (regulating its mitophagy receptor function); Enhancement or inhibition of FUNDC1-mediated mitophagy (for mitochondrial quality control, particularly in cardiac or hypoxic contexts)