Tohoku J. Exp. Med., 2003, 200 (1)

The Long, but not the Short, Presequence of Human
Coproporphyrinogen Oxidase is Essential for
Its Import and Sorting to Mitochondria

SHINJI SUSA,^1,2 MAKOTO DAIMON,¹ HIDEYU ONO,² SONG LI,²
TADASHI YOSHIDA² and TAKEO KATO¹

¹The Third Department of Internal Medicine,
²The Department of Biochemistry, Yamagata University School of Medicine, Yamagata 990-9585

Nucleotide sequence analyses of human coproporphyrinogen oxidase (CPO) have shown two possible translation initiation codons (TICs) in the region upstream from the region coding the mature polypeptide. These TICs lead to the precursor polypeptides of CPO (long and short pCPOs), which have 110 and 10 amino acids (long and short) presequences, respectively. To determine which TIC is the real one, import reactions to mitochondria of the two pCPOs synthesized using in vitro transcription-translation system were analyzed. The results showed that the long pCPO was imported into mitochondria and sorted properly to the intermembrane space, whereas the short pCPO was not. We also found several miss-readings in the reported nucleotide sequence of mouse CPO gene. This correction revealed that mouse pCPO has also a longer presequence, which are very similar to the long presequence of human. These results indicate that the long, but not short, presequence is the real one.

keywords —— human coproporphyrinogen oxidase; presequence; mitochondrial import

© 2003 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2003, 200, 39-45

Address for reprints: Makoto Daimon, M.D., The Third Department of Internal Medicine, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.

e-mail: mdaimon@med.id.yamagata-u.ac.jp