Regulatory mechanisms for heme biosynthesis in response to the change of regulatory heme pool.

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Heme is an essential prosthetic group of several proteins, and is synthesized in all living cells. On the other hand, production of heme was strictly regulated in each cells, since excess amount of heme produces reactive oxygen spices. It has been well known that the expression of non-specific 5-aminolevulinate synthase (ALAS1), which is the first and the rate limiting enzyme of heme biosynthetic pathway in non-erythroid cells, is regulated at transcriptional, as well as at several post-transcriptional levels for the strict regulation of heme biosynthesis. In the present project, we have challenged to determine the novel mechanisms, which is involved in the precise and quick response of ALAS1 expression to the change of heme contents in the cells.As a result, we have successfully identified novel mechanisms for post-translational regulation of ALAS1 protein in mitochondria.