Utilization of Cytochrome b562 as a Localized Labile Heme Chelator

Abstract

Heme is an essential, but toxic cofactor required for virtually all aerobic life. As a consequence, cells are challenged to safely traffic heme to hemoproteins that reside in every subcellular compartment. However, the mechanisms underlying heme transport and trafficking are largely unknown. Moreover, it is unclear how various subcellular compartments communicate their requirement for heme to the mitochondria, where heme is synthesized. In order to determine how different subcellular compartments sense and respond to heme deficiency, I have been developing a heme chelator to induce local heme deficiencies. Once this is achieved, we can employ transcriptome and proteome profiling to determine pathways that enable various organelles to adapt to heme deficiency. Altogether, we seek to better understand how cells appropriate and distribute heme to diverse compartments that require this essential nutrient.