FUN14 domain-containing protein 1 (FUNDC1)

FUN14 domain-containing protein 1 is an **outer mitochondrial membrane protein** that acts as a **receptor for mitophagy**, the selective autophagic clearance of damaged mitochondria[7][4][1]. It contains three α-helical transmembrane domains, with its LIR motif binding directly to the autophagy protein LC3, thus initiating mitophagy especially under hypoxic or stress conditions[7]. FUNDC1 plays a central role in maintaining mitochondrial quality and cellular health, linking mitochondrial dynamics (fission/fusion) and apoptotic regulation. It also contributes to the formation of mitochondria-associated endoplasmic reticulum membranes (MAMs), impacting processes such as calcium signaling and angiogenesis[3]. **Dysfunction or altered expression of FUNDC1** is implicated in cardiovascular disease, cancer, and metabolic disorders, and its activity is tightly regulated by phosphorylation and ubiquitination[1][6][7]. Although not a traditional drug target, its central role in mitochondrial homeostasis represents a potential therapeutic avenue for conditions driven by mitophagy imbalance.

Other names

FUNDC1FUN14 domain containing 1FUN14 domain-containing 1

Agents that affect FUNDC1 typically act by modulating its phosphorylation/dephosphorylation or ubiquitination, thereby regulating mitophagy activity[1][7]. Indirect mechanisms may involve influencing interactions with proteins such as LC3 (binding through the LIR motif), DRP1 (regulating mitochondrial fission), or elements of the endoplasmic reticulum.[7][3]