The von Hippel-Lindau tumor suppressor targets to mitochondrial

Subcellular localization of von Hippel-Lindau (VHL) tumor suppressor may cl arify its role in tumorigenesis. In rat kidney, we observed a granular cyto plasmic immunostaining of VHL, as seen in human tissues. The green fluoresc ent protein (GFP)-tagged VHL also appeared as cytoplasmic granules in vitro and was colocalized with a mitochondrion-selective dye. Immunogold electro n microscopy localized VHL specifically to the mitochondrion. Mitochondria retaining GFP-VHL fusion protein, mimicking an insertional VHL mutant, disp layed abnormal phenotypes. Among these, small mitochondria have been observ ed in clear cell renal carcinomas known to have frequent VHL alterations. T hus, VHL may contribute to tumorigenesis through mitochondria-based action.