Heme must be synthesized and degraded within an individual nucleated cell. Heme 
degradation is catalyzed by the two isozymes of heme oxygenase, heme oxygenase-1 
(HO-1) and HO-2, eventually yielding biliverdin/bilirubin, CO, and iron. These 
products possess important physiological roles but are potentially toxic to 
cells. Characteristically, human HO-1 contains no Cys residues, whereas HO-2 
contains the potential heme-binding motifs of the Cys-Pro dipeptide. Expression 
of HO-1 is inducible or repressible, depending on cell types or cellular 
microenvironments, but expression levels of HO-2 are fairly constant. Thus, the 
main regulation of heme catabolism is a problem of the balance between induction 
and repression of HO-1. Notably, HO-1 expression is induced by heme in all 
mammalian cells examined, but is repressed by hypoxia in certain types of 
cultured human cells. The recent discovery of Bach1 as a heme-regulated and 
hypoxia-inducible repressor for transcription of the HO-1 gene has provided a 
missing link in the feedback control of heme catabolism. On the other hand, the 
human HO-1 gene promoter contains the (GT)n repeat polymorphism and a single 
nucleotide polymorphism (-427A --> T), both of which may contribute to 
fine-tuning of the transcription. Importantly, long (GT)n alleles are associated 
with susceptibility to smoking-induced emphysema or coronary artery disease, but 
may provide with resistance to cerebral malaria. The latter finding suggests a 
novel therapeutic strategy with inhibitors of HO-1 for the treatment of cerebral 
malaria. We discuss the potential regulatory role of Bach1 and HO-2 in heme 
catabolism and update the understanding of the regulation of HO-1 expression.