F1FoATP synthase (
ATP synthase) is a ubiquitous
enzyme complex in eukaryotes. In general it is localized to the mitochondrial inner membrane and serves as the last step in the mitochondrial oxidative phosphorylation of
ADP to
ATP, utilizing a
proton gradient across the inner mitochondrial membrane built by the complexes of the electron transfer chain. However some cell types, including
tumors, carry
ATP synthase on the cell surface. It was suggested that cell surface
ATP synthase helps
tumor cells thriving on glycolysis to survive their high
acid generation.
Angiostatin,
aurovertin,
resveratrol, and
antibodies against the α and β subunits of
ATP synthase were shown to bind and selectively inhibit cell surface
ATP synthase, promoting
tumor cell death. Here we show that
ATP synthase β (ATP5B) is present on the cell surface of mouse
pheochromocytoma cells as well as
tumor cells of human SDHB-derived
paragangliomas (PGLs), while being virtually absent on chromaffin primary cells from bovine adrenal medulla by confocal microscopy. The cell surface location of ATP5B was verified in the tissue of an SDHB-derived PGL by immunoelectron microscopy. Treatment of mouse
pheochromocytoma cells with
resveratrol as well as ATP5B antibody led to statistically significant proliferation inhibition. Our data suggest that PGLs carry
ATP synthase on their surface that promotes cell survival or proliferation. Thus, cell surface
ATP synthase may present a novel therapeutic target in treating metastatic or inoperable PGLs.