FUN14 domain-containing protein 2 (FUNDC2)

FUN14 domain-containing protein 2 (FUNDC2) is a highly conserved, ubiquitously expressed mitochondrial outer membrane protein characterized by two or three transmembrane domains. It plays critical roles in regulating ferroptosis (iron-dependent programmed necrosis) via interaction with the mitochondrial glutathione transporter SLC25A11, affecting glutathione metabolism and cellular susceptibility to lipid peroxidation and oxidative stress. FUNDC2 is necessary for platelet survival under stress and interacts directly with the lipid PIP3 through a conserved N-terminal motif, modulating AKT and BAD phosphorylation and supporting cell survival pathways. It is implicated in several disease contexts including doxorubicin-induced cardiomyopathy (where its knockout offers protection), cancers (serving as a proto-oncogene, with levels correlating to prognosis and immune infiltration), and potential roles in viral infection and cell death regulation. Targeting FUNDC2 therapeutically, especially in ferroptosis-related diseases, holds research interest, but broad mitochondrial and cell viability effects must be carefully considered.

Other names

HCBP6DC44HCC3PD03104HCC-3Cervical cancer proto-oncogene 3 proteinHepatitis C virus core-binding protein 6cervical cancer oncogene 3

For doxorubicin: Doxorubicin induces ferroptosis in cardiomyocytes, and knockout or inhibition of FUNDC2 protects against this by regulating mitochondrial glutathione levels. Potential indirect relevance for ferroptosis inhibitors and drugs modulating mitochondrial function