Abstract
Heme is a ubiquitous and essential iron containing metallo-organic cofactor required for virtually all aerobic life. Heme synthesis is initiated and completed in mitochondria, followed by certain covalent modifications and/or its delivery to apo-hemoproteins residing throughout the cell. While the biochemical aspects of heme biosynthetic reactions are well understood, the trafficking of newly synthesized heme—a highly reactive and inherently toxic compound—and its subsequent delivery to target proteins remain far from clear. In this review, we summarize current knowledge about heme biosynthesis and trafficking within and outside of the mitochondria.
Highlights
Heme b, or iron protoporphyrin IX (Fe-PPIX), is an essential but potentially cytotoxic protein prosthetic group and signaling molecule
Found that disruption of the adenine nucleotide translocator (ANT) genes in yeast (AAC1, PET9 and AAC3) resulted in a reduction of heme biosynthesis via blockage of precursors from entering the matrix. These transporters may play certain role in tetrapyrroles transport to PPOX and/or FECH. These findings suggest that ATP:ADP ratios, mitochondrial protonmotive force and cellular energy status may regulate heme synthesis in response to changes in metabolic demand further studies are warranted to elucidate this issue
We recently showed that Pet117 is the mitochondrial protein localized to the matrix side of the inner mitochondrial membrane (IMM) [148]
Summary
Iron protoporphyrin IX (Fe-PPIX), is an essential but potentially cytotoxic protein prosthetic group and signaling molecule. RNA processing proteins [5,7,8,9] or its catabolism to the signaling molecule, carbon monoxide (CO), collectively regulate diverse physiological processes that include oxygen sensing, iron homeostasis, the oxidative stress response, mitochondrial respiration and biogenesis, mitophagy, apoptosis, circadian rhythms, cell cycle progression and proliferation [1,7,10,11,12,13,14,15,16,17,18,19] Another vital role for heme b is to act as a precursor for the synthesis of other heme types important for eukaryotic physiology, including hemes c, o and a (Figure 1)
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