ATPase family AAA domain-containing protein 3A (ATAD3A)–Voltage-dependent anion-selective channel protein 1 (VDAC1) protein–protein interface (ATAD3A–VDAC1 interface)

The ATAD3A–VDAC1 protein–protein interface is a critical regulatory site located at the contact points between the inner and outer mitochondrial membranes (PubMed: 28416610). ATPase family AAA domain-containing protein 3A (ATAD3A) is an essential mitochondrial enzyme involved in nucleoid organization and cholesterol transport (UniProt Q9NVI7), while Voltage-dependent anion-selective channel protein 1 (VDAC1) is the primary gatekeeper for metabolites across the outer mitochondrial membrane (UniProt P21796). The interaction between these two proteins facilitates the transfer of cholesterol into the mitochondria, a process often hijacked by cancer cells to support rapid proliferation and evade apoptosis (PubMed: 31582744). In particular, the ATAD3A–VDAC1 complex is highly expressed in glioblastoma and breast cancer, where it contributes to chemoresistance and tumor progression (PubMed: 28416610). Therapeutic strategies targeting this interface, such as the peptide inhibitor DA-ATAD3-7, aim to disrupt this interaction to restore apoptotic sensitivity and inhibit tumor growth (PubMed: 31582744). Beyond oncology, dysregulation of this interface is implicated in neurodegenerative and mitochondrial diseases, making it a versatile target for drug development (PubMed: 25605871).

Other names

ATAD3A-VDAC1 complexATAD3A-VDAC1 interactionATAD3A-VDAC1 PPI

Inhibition of the protein-protein interaction between ATAD3A and VDAC1 to disrupt mitochondrial cholesterol trafficking and induce apoptosis (PubMed: 31582744).