Adenine nucleotide translocator transports haem precursors into mitochondria

Motoki Azuma, Yasuaki Kabe, Chikanori Kuramori, Masao Kondo, Yuki Yamaguchi, Hiroshi Handa

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Haem is a prosthetic group for haem proteins, which play an essential role in oxygen transport, respiration, signal transduction, and detoxification. In haem biosynthesis, the haem precursor protoporphyrin IX (PP IX) must be accumulated into the mitochondrial matrix across the inner membrane, but its mechanism is largely unclear. Here we show that adenine nucleotide translocator (ANT), the inner membrane transporter, contributes to haem biosynthesis by facilitating mitochondrial accumulation of its precursors. We identified that haem and PP IX specifically bind to ANT. Mitochondrial uptake of PP IX was inhibited by ADP, a known substrate of ANT. Conversely, ADP uptake into mitochondria was competitively inhibited by haem and its precursors, suggesting that haem-related porphyrins are accumulated into mitochondria via ANT. Furthermore, disruption of the ANT genes in yeast resulted in a reduction of haem biosynthesis by blocking the translocation of haem precursors into the matrix. Our results represent a new model that ANT plays a crucial role in haem biosynthesis by facilitating accumulation of its precursors into the mitochondrial matrix.

Original languageEnglish
Article numbere3070
JournalPLoS One
Volume3
Issue number8
DOIs
Publication statusPublished - 2008 Aug 27

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Mitochondria
Adenine Nucleotides
Heme
mitochondria
protoporphyrin
biosynthesis
Biosynthesis
uptake mechanisms
porphyrins
Adenosine Diphosphate
transporters
signal transduction
adenine nucleotides
yeasts
Signal transduction
Detoxification
oxygen
Membrane Transport Proteins
Porphyrins
Prosthetics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Adenine nucleotide translocator transports haem precursors into mitochondria. / Azuma, Motoki; Kabe, Yasuaki; Kuramori, Chikanori; Kondo, Masao; Yamaguchi, Yuki; Handa, Hiroshi.

In: PLoS One, Vol. 3, No. 8, e3070, 27.08.2008.

Research output: Contribution to journalArticle

Azuma, Motoki ; Kabe, Yasuaki ; Kuramori, Chikanori ; Kondo, Masao ; Yamaguchi, Yuki ; Handa, Hiroshi. / Adenine nucleotide translocator transports haem precursors into mitochondria. In: PLoS One. 2008 ; Vol. 3, No. 8.
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