Similarly the mitochondrial IMS protein coiled-coil helix domain containing protein 4 (CHCHD4, Mia40 in yeast) has also been shown to stimulate mitochondrial perinuclear clustering, and thus intracellular oxygenation, in a HIF-1α-dependent manner in U2OS osteosarcoma cells [125]. The gene discussed is CHCHD4; the disease is osteosarcoma.