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

The ATPase family AAA domain-containing protein 3A (ATAD3A) and Voltage-dependent anion-selective channel protein 1 (VDAC1) form a critical regulatory complex at the mitochondrial membrane contact sites (UniProt Q9NVI7, P21796). This complex plays a pivotal role in maintaining mitochondrial structural integrity, regulating the transport of metabolites like ATP and calcium, and managing mitochondrial DNA (mtDNA) stability (PubMed: 28211449). It acts as a bridge between the inner and outer mitochondrial membranes, influencing the mitochondrial permeability transition pore (mPTP) and overall organelle dynamics. In neurodegenerative disorders such as Alzheimer's disease, the ATAD3A-VDAC1 interaction is pathologically enhanced, contributing to mitochondrial fragmentation, impaired bioenergetics, and neuronal death (PubMed: 35110310). Conversely, in various cancers, the complex supports the metabolic demands of rapidly proliferating cells and provides resistance to apoptosis by stabilizing the mitochondrial outer membrane (PubMed: 31558662). Experimental therapeutic approaches involve the use of small molecules or synthetic peptides, such as TAT-ATAD3A, designed to disrupt the ATAD3A-VDAC1 interface, thereby normalizing mitochondrial dynamics or sensitizing cancer cells to treatment (PubMed: 35110310). However, the essential role of these proteins in basal cellular respiration and steroidogenesis poses a significant challenge for drug development, necessitating precise targeting to minimize adverse effects on healthy tissues (PubMed: 22532568).

Other names

ATAD3A-VDAC1 interactionATAD3A/VDAC1 complexATAD3A-VDAC1-HKII complex

Disruption of the protein-protein interaction to prevent mitochondrial dysfunction and apoptosis.