TY - JOUR
T1 - Brain mitochondria contain aquaporin water channels
T2 - Evidence for the expression of a short AQP9 isoform in the inner mitochondrial membrane
AU - Amiry-Moghaddam, Mahmood
AU - Lindland, Heidi
AU - Zelenin, Sergey
AU - Roberg, Bjørg Å
AU - Gundersen, Brigitta B.
AU - Petersen, Petur
AU - Rinvik, Eric
AU - Torgner, Ingeborg A.
AU - Ottersen, Ole P.
PY - 2005/9
Y1 - 2005/9
N2 - 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 AQP9-an aquaglyceroporin with a particularly broad substrate specificity-and 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 Parkinson's disease.
AB - 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 AQP9-an aquaglyceroporin with a particularly broad substrate specificity-and 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 Parkinson's disease.
KW - Astrocytes
KW - Mitochondria
KW - Parkinson's disease
KW - Substantia nigra
KW - Water channels
UR - http://www.scopus.com/inward/record.url?scp=24644521470&partnerID=8YFLogxK
U2 - 10.1096/fj.04-3515com
DO - 10.1096/fj.04-3515com
M3 - Article
C2 - 16126913
AN - SCOPUS:24644521470
SN - 0892-6638
VL - 19
SP - 1459
EP - 1467
JO - FASEB Journal
JF - FASEB Journal
IS - 11
ER -