Adenine nucleotide translocator transports haem precursors into mitochondria.
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.
Azuma
Motoki
M
Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama, Japan.
Kabe
Yasuaki
Y
Kuramori
Chikanori
C
Kondo
Masao
M
Yamaguchi
Yuki
Y
Handa
Hiroshi
H
D000818:Animals; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006420:Hemeproteins / Q000378:metabolism; D007700:Kinetics; D008930:Mitochondria, Liver / Q000201:enzymology*; D000226:Mitochondrial ADP, ATP Translocases / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008970:Molecular Weight; D011487:Protein Conformation; D011524:Protoporphyrins / Q000378:metabolism; D051381:Rats
D006420:Hemeproteins; D011524:Protoporphyrins; D006418:Heme; D000226:Mitochondrial ADP, ATP Translocases; C028025:protoporphyrin IX