An unlikely heme chaperone confirmed at last

Abstract

Labile heme, as opposed to heme that is tightly bound within proteins, is thought to require a chaperone to be trafficked within the cell due to its cytotoxicity, but the identity of this chaperone was not known. A new study reveals that an unlikely protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is a heme chaperone that binds and transfers labile heme to downstream target proteins. These results provide a new framework for understanding heme homeostasis and raise intriguing questions regarding the intersection of heme transport, carbohydrate metabolism, and intracellular signaling.

Figure 1.

Model of GAPDH as a heme chaperone that sequesters and transfers bioavailable heme to target hemeproteins. Heme can be synthesized endogenously from δ-ALA (aminolevulinic acid) or imported from exogenous sources through the plasma membrane. Sweeny et al. (2) demonstrate that GAPDH can bind both exogenous and endogenously generated heme and make heme bioavailable to target proteins. They also show that GAPDH-bound heme can be delivered to soluble proteins such as iNOS or to nuclear proteins such as the transcription factor Hap1p. There are likely heme chaperones other than GAPDH to interact with the many cellular target proteins.