Lysosomal membrane ascorbate-dependent ferrireductase CYB561A3 (CYB561A3)

Lysosomal membrane ascorbate-dependent ferrireductase CYB561A3 is a transmembrane enzyme of the cytochrome b561 family, encoded by the CYB561A3 gene. It mediates ascorbate-dependent electron transport across lysosomal and endosomal membranes, using ascorbic acid (vitamin C) as an electron donor to reduce ferric iron (Fe³⁺) to ferrous iron (Fe²⁺). This reduction is a key step enabling iron export from lysosomes and is essential for maintaining intracellular iron homeostasis. CYB561A3 is especially important in certain cell types, such as Burkitt lymphoma cells, in which its depletion causes iron starvation, lysosomal and mitochondrial dysfunction, and impaired proliferation—defects that can be rescued by ascorbate or direct iron supplementation. Its expression has been linked to immune defense mechanisms in macrophages as well as to dysregulated states in various diseases, highlighting CYB561A3 as both a potential therapeutic target and a biomarker for iron metabolism disorders

Other names

Lysosomal membrane ascorbate-dependent ferrireductase CYB561A3CYB561A3CYBASC3PSEC0259LCytbLCYTBCytochrome b ascorbate-dependent protein 3Cytochrome b561 family member A3Lysosomal cytochrome bLysosomal cytochrome b561Lysosomal membrane ascorbate-dependent ferrireductasecytochrome b, ascorbate dependent 3

Drugs targeting CYB561A3 would be expected to modulate ferrireductase activity, affecting lysosomal iron reduction and cellular iron availability