Heme allocation in eukaryotic cells relies on mitochondrial heme export through FLVCR1b to cytosolic GAPDH. Nat Commun 2025 Aug 26;16(1):7972
Date
08/28/2025Pubmed ID
40858607Pubmed Central ID
PMC12381273DOI
10.1038/s41467-025-62819-2Scopus ID
2-s2.0-105014169951 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
Heme is an iron-containing cofactor generated in mitochondria that must leave this organelle to reach protein targets in other cell compartments. Because mitochondrial heme binding by cytosolic GAPDH enables its distribution in cells, we sought to uncover how heme reaches GAPDH. Experiments utilizing two human cell lines and a GAPDH reporter protein whose heme binding can be followed by fluorescence reveal that the mitochondrial protein FLVCR1b provides heme to GAPDH in concert with a rise and fall in their association. An absence of FLVCR1b diminishes GAPDH association with mitochondria and prevents GAPDH and cell hemeproteins from receiving heme. GAPDH heme procurement also requires the TANGO2 protein, which interacts with FLVCR1b to presumably support heme export. In isolated mitochondria, GAPDH associates with FLVCR1b to trigger heme release and delivery to client hemeproteins. Identifying FLVCR1b as the source of mitochondrial heme for GAPDH reveals a path by which this essential cofactor can reach multiple protein targets within eukaryotic cells.
Author List
Jayaram DT, Sivaram P, Biswas P, Dai Y, Sweeny EA, Stuehr DJAuthor
Elizabeth Sweeny PhD Assistant Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
CytosolGlyceraldehyde-3-Phosphate Dehydrogenases
Heme
Humans
Membrane Transport Proteins
Mitochondria
Protein Binding
Receptors, Virus
