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* Centre for Molecular Biology and Neuroscience, and
Nordic Centre for Water Imbalance Related Disorders (WIRED), and
¶ Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; and
# Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden
1 Correspondence: Centre for Molecular Biology and Neuroscience, University of Oslo, P.O. Box 1105 Blindern, N-0317 Oslo, Norway. E-mail: mahmo{at}medisin.uio.no
Aquaporins are a family of water channels found in animals, plants, and microorganisms. A subfamily of aquaporins, the aquaglyceroporins, are permeable for water as well as certain solutes such as glycerol, lactate, and urea. Here we show that the brain contains two isoforms of AQP9an aquaglyceroporin with a particularly broad substrate specificityand that the more prevalent of these isoforms is expressed in brain mitochondria. The mitochondrial AQP9 isoform is detected as an
25 kDa band in immunoblots. This isoform is likely to correspond to a new AQP9 mRNA that is obtained by alternative splicing and has a shorter ORF than the liver isoform. Subfractionation experiments and high-resolution immunogold analyses revealed that this novel AQP9 isoform is enriched in mitochondrial inner membranes. AQP9 immunopositive mitochondria occurred in astrocytes throughout the brain and in a subpopulation of neurons in the substantia nigra, ventral tegmental area, and arcuate nucleus. In the latter structures, the AQP9 immunopositive mitochondria were located in neurons that were also immunopositive for tyrosine hydroxylase, as demonstrated by double labeling immunogold electron microscopy. Our findings suggest that mitochondrial AQP9 is a hallmark of astrocytes and midbrain dopaminergic neurons. In physiological conditions, the flux of lactate and other metabolites through AQP9 may confer an advantage by allowing the mitochondria to adjust to the metabolic status of the extramitochondrial cytoplasm. We hypothesize that the complement of mitochondrial AQP9 in dopaminergic neurons may relate to the vulnerability of these neurons in Parkinsons disease.Amiry-Moghaddam, M., Lindland, H., Zelenin, S., Roberg, B. A., Gundersen, B. B., Petersen, P., Rinvik, R., Torgner, I. A., Ottersen, O. P. Brain mitochondria contain aquaporin water channels: evidence for the expression of a short AQP9 isoform in the inner mitochondrial membrane.
Key Words: water channels mitochondria Parkinsons disease astrocytes substantia nigra
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