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 it...

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Autores principales:	Motoki Azuma, Yasuaki Kabe, Chikanori Kuramori, Masao Kondo, Yuki Yamaguchi, Hiroshi Handa
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bbb2c7af426d478cace38344c5a8c6f9
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spelling	oai:doaj.org-article:bbb2c7af426d478cace38344c5a8c6f92021-11-25T06:18:50ZAdenine nucleotide translocator transports haem precursors into mitochondria.1932-620310.1371/journal.pone.0003070https://doaj.org/article/bbb2c7af426d478cace38344c5a8c6f92008-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18728780/?tool=EBIhttps://doaj.org/toc/1932-6203Haem 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.Motoki AzumaYasuaki KabeChikanori KuramoriMasao KondoYuki YamaguchiHiroshi HandaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 8, p e3070 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Motoki Azuma Yasuaki Kabe Chikanori Kuramori Masao Kondo Yuki Yamaguchi Hiroshi Handa Adenine nucleotide translocator transports haem precursors into mitochondria.
description	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.
format	article
author	Motoki Azuma Yasuaki Kabe Chikanori Kuramori Masao Kondo Yuki Yamaguchi Hiroshi Handa
author_facet	Motoki Azuma Yasuaki Kabe Chikanori Kuramori Masao Kondo Yuki Yamaguchi Hiroshi Handa
author_sort	Motoki Azuma
title	Adenine nucleotide translocator transports haem precursors into mitochondria.
title_short	Adenine nucleotide translocator transports haem precursors into mitochondria.
title_full	Adenine nucleotide translocator transports haem precursors into mitochondria.
title_fullStr	Adenine nucleotide translocator transports haem precursors into mitochondria.
title_full_unstemmed	Adenine nucleotide translocator transports haem precursors into mitochondria.
title_sort	adenine nucleotide translocator transports haem precursors into mitochondria.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/bbb2c7af426d478cace38344c5a8c6f9
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_version_	1718413948424814592

Adenine nucleotide translocator transports haem precursors into mitochondria.

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