Key roles of GAPDH, Hsp90, and NO in heme trafficking.

Intracellular trafficking of mitochondrial heme to create functional heme proteins presents a fundamental challenge in animal cells. This article provides some background on heme allocation, discusses some of the concepts, and then reviews research from the last two decades that has uncovered unexpected and important roles for glyceraldehyde 3-phosphate dehydrogenase (GAPDH), heat shock protein 90 (Hsp90), and nitric oxide (NO) in enabling and regulating cell heme allocations to hemeproteins that mature and function outside of the mitochondria. A model for how hemeprotein heme contents and functions in cells can be regulated through the coordinate participation of GAPDH, Hsp90, and NO is presented.