Dr. Molly Sutherland
University of Delaware
Friday, April 3, 2026
12:00 Noon
Room 120 – Meyerhoff Chemistry Building
Host: Dr. Aaron Smith
“How does heme move? Insights into heme trafficking from the bacterial cytochrome c biogenesis pathways”
Heme is a critical cofactor for many biological processes across all domains of life. Heme’s redox properties contribute to its functions in gas sensing, electron transfer, as well regulation of key cellular processes. Yet, the same redox properties that confer heme’s biological importance also render it highly cytotoxic resulting in tight intracellular regulation. Despite its biological relevance, the molecular mechanisms of heme transport are not well understood. We are developing the bacterial cytochrome c biogenesis pathways as model to probe the binding, transport and modification of heme. Cytochromes c are widespread hemoproteins that commonly function in the context of electron transport chains to support respiration, photosynthesis and even detoxification. All cytochromes c require the covalent attachment of heme for proper folding and function. Heme attachment or cytochrome c biogenesis requires the trafficking of heme from the inside to the outside of the cell where heme is stereospecifically positioned by the holocytochrome c synthase and attached to cytochrome c. Three pathways for cytochrome c biogenesis have been identified: System I (prokaryotes, CcmABCDEFGH/I), System II (prokaryotes, CcsBA or ResBC) and System III (eukaryotes, HCCS). We use a well-characterized recombinant E. coli system for functional assays and affinity purification of pathway components with endogenous heme to interrogate heme trafficking mechanisms. Structure-function analyses have biochemically mapped a conserved heme binding domain which may represent a novel antimicrobial target. Recently, a heme transport channel has been identified, providing insights into general mechanisms of heme trafficking.