HEM15

HEM15 is a gene in the budding yeast Saccharomyces cerevisiae that encodes ferrochelatase, the final enzyme in the mitochondrial heme biosynthesis pathway. The enzyme catalyzes the chelation of ferrous iron (Fe2+) into protoporphyrin IX to form heme B, a prosthetic group essential for a wide range of hemoproteins.

Localization and gene product: The HEM15-encoded ferrochelatase is synthesized with an N-terminal mitochondrial targeting sequence and is imported into mitochondria, where it associates with the inner mitochondrial membrane to complete the last step of heme synthesis. The enzyme is functionally conserved across eukaryotes and bacteria, typically operating as the final, rate-limiting step in the pathway.

Biological role: Heme produced by HEM15 is required for the proper function of respiratory electron transport chain complexes and other mitochondrial processes. Defects in HEM15 can lead to reduced respiratory capacity, impaired growth on non-fermentable carbon sources, and accumulation of porphyrin intermediates that can be cytotoxic under certain conditions.

Regulation and interactions: Expression of HEM15 is coordinated with other heme biosynthetic genes and responds to cellular heme levels and oxygen availability. In yeast, regulatory networks involving heme-responsive transcription factors contribute to balancing heme production with cellular demand.

Evolutionary context: HEM15 is the yeast ortholog of bacterial hemH and vertebrate FECH, reflecting the conserved chemistry of ferrochelatase across domains of life. Structural and functional similarities support the shared mechanism of iron insertion into protoporphyrin IX.

Research relevance: Studying HEM15 informs understanding of mitochondrial heme biosynthesis, porphyrin metabolism, and the integration of heme production with cellular respiration.