Porphyrin accumulation in mitochondria is mediated by 2-oxoglutarate carrier

Yasuaki Kabe, Masashi Ohmori, Kazuya Shinouchi, Yasunori Tsuboi, Satoshi Hirao, Motoki Azuma, Hajime Watanabe, Ichiro Okura, Hiroshi Handa

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Heme (Fe-protoporphyrin IX), an endogenous porphyrin derivative, is an essential molecule in living aerobic organisms and plays a role in a variety of physiological processes such as oxygen transport, respiration, and signal transduction. For the biosynthesis of heme or the mitochondrial heme proteins, heme or its biosynthetic precursor porphyrin must be transported into mitochondria from cytosol. The mechanism of porphyrin accumulation in the mitochondrial inner membrane is unclear. In the present study, we analyzed the mechanism of mitochondrial translocation of porphyrin derivatives. We showed that palladium meso-tetra(4-carboxyphenyl)porphyrin (PdTCPP), a phosphorescent porphyrin derivative, accumulated in the mitochondria of several cell lines. Using affinity latex beads, we showed that 2-oxoglutarate carrier (OGC), the mitochondrial transporter of 2-oxoglutarate, bound to PdTCPP, and in vitro PdTCPPinhibited 2-oxoglutarate uptake into mitochondria in a competitive manner (Ki = 15 μM). Interestingly, all types of porphyrin derivatives examined in this study competitively inhibited 2-oxoglutarate uptake into mitochondria, including protoporphyrin IX, coproporphyrin III, and hemin. Furthermore, mitochondrial accumulation of porphyrins was inhibited by 2-oxoglutarate or OGC inhibitor. These results suggested that porphyrin accumulation in mitochondria is mediated by OGC and that porphyrins are able to competitively inhibit 2-oxoglutarate uptake into mitochondria. This is the first report of a putative mechanism for accumulation of porphyrins in the mitochondrial inner membrane.

Original languageEnglish
Pages (from-to)31729-31735
Number of pages7
JournalJournal of Biological Chemistry
Volume281
Issue number42
DOIs
Publication statusPublished - 2006 Oct 20
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Porphyrin accumulation in mitochondria is mediated by 2-oxoglutarate carrier'. Together they form a unique fingerprint.

Cite this