Mitochondrial ATP transporter Ant2 depletion impairs erythropoiesis and B lymphopoiesis

J. Cho, J. Seo, C. H. Lim, L. Yang, T. Shiratsuchi, M. H. Lee, R. R. Chowdhury, H. Kasahara, J. S. Kim, S. P. Oh, Y. J. Lee, N. Terada

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Adenine nucleotide translocases (ANTs) transport ADP and ATP through mitochondrial inner membrane, thus playing an essential role for energy metabolism of eukaryotic cells. Mice have three ANT paralogs, Ant1 (Slc25a4), Ant2 (Slc25a5) and Ant4 (Slc25a31), which are expressed in a tissue-dependent manner. While knockout mice have been characterized with Ant1 and Ant4 genes, which resulted in exercise intolerance and male infertility, respectively, the role of the ubiquitously expressed Ant2 gene in animal development has not been fully demonstrated. Here, we generated Ant2 hypomorphic mice by targeted disruption of the gene, in which Ant2 expression is largely depleted. The mice showed apparently normal embryonic development except pale phenotype along with a reduced birth rate. However, postnatal growth was severely retarded with macrocytic anemia, B lymphocytopenia, lactic acidosis and bloated stomach, and died within 4 weeks. Ant2 depletion caused anemia in a cell-autonomous manner by maturation arrest of erythroid precursors with increased reactive oxygen species and premature deaths. B-lymphocyte development was similarly affected by Ant2 depletion, and splenocytes showed a reduction in maximal respiration capacity and cellular ATP levels as well as an increase in cell death accompanying mitochondrial permeability transition pore opening. In contrast, myeloid, megakaryocyte and T-lymphocyte lineages remained apparently intact. Erythroid and B-cell development may be particularly vulnerable to Ant2 depletion-mediated mitochondrial dysfunction and oxidative stress.

Original languageEnglish
Pages (from-to)1437-1450
Number of pages14
JournalCell Death and Differentiation
Issue number9
StatePublished - Sep 11 2015


Dive into the research topics of 'Mitochondrial ATP transporter Ant2 depletion impairs erythropoiesis and B lymphopoiesis'. Together they form a unique fingerprint.

Cite this