ATP6V1D Full Name
ATPase, H+ transporting, lysosomal 34kDa, V1 subunit D
ATP6V1D Introduction
ATP6V1D is an essential structural and functional component of the vacuolar-type H+-ATPase (V-ATPase) complex, a massive molecular motor responsible for acidifying intracellular compartments. Within this complex, ATP6V1D functions as subunit D of the cytosolic V1 domain. Together with subunit F, it forms the critical "central rotor stalk." This structural axis physically and mechanically couples the ATP-hydrolyzing hexameric ring of the V1 domain (subunits A and B) to the membrane-embedded V0 proton channel. As ATP is hydrolyzed, the central stalk rotates, driving the continuous translocation of protons (H+) against their concentration gradient into the lysosomal lumen. This finely tuned, ATP-driven acidification is absolutely necessary for maintaining cellular pH homeostasis, facilitating autophagosome-lysosome fusion, and ensuring the efficient proteolytic degradation of sequestered cargo within the autophagy-lysosome pathway.
Figure 1. The structure diagram of V-ATPase in insects. (Source: Liu X, et al. 2025)
Clinically, the dysregulation of ATP6V1D is deeply intertwined with cancer progression, metabolic diseases, and host immune responses. In the context of oncology, ATP6V1D acts as a critical metabolic regulator and oncogenic driver in hepatocellular carcinoma (HCC). Cancer stem cells frequently upregulate ATP6V1D to aggressively maintain their autophagic flux. By hyper-acidifying lysosomes and actively facilitating the assembly of the ESCRT-III complex, ATP6V1D ensures rapid autophagosome-lysosome fusion, thereby fueling tumor stemness, survival, and malignant progression in nutrient-deprived microenvironments. Conversely, in metabolic disorders such as steatohepatitis, the detrimental downregulation of ATP6V1D impairs lysosomal acidification, leading to severe autophagic dysfunction and cellular stress. Beyond non-communicable diseases, ATP6V1D plays a synergistic role in innate immunity. During intracellular parasitic infections, such as by Toxoplasma gondii, host macrophages actively upregulate ATP6V1D to rapidly acidify lysosomes. This enhances the activation of hydrolytic enzymes to restrict pathogen proliferation. Consequently, whether targeting its overexpression in aggressive liver cancers or exploring its role in infectious diseases, ATP6V1D represents a highly dynamic and promising therapeutic target.
Alternate Names for ATP6V1D
ATP6V1D
ATPase, H+ transporting, lysosomal 34kDa, V1 subunit D
VATD
VMA8
ATP6M
V-type proton ATPase subunit D
V-ATPase D subunit
V-ATPase subunit D
vacuolar H-ATPase subunit D
vacuolar proton pump D subunit
