The Inner Mitochondrial Membrane Has Aquaporin-8 Water Channels and Is Highly Permeable to Water

Abstract

Mitochondria are remarkably plastic organelles constantly changing their shape to fulfil their various functional activities. Although the osmotic movement of water into and out of the mitochondrion is central for its morphology and activity, the molecular mechanisms and the pathways for water transport across the inner mitochondrial membrane (IMM), the main barrier for molecules moving into and out of the organelle, are completely unknown. Here, we show the presence of a member of the aquaporin family of water channels, AQP8, and demonstrate the strikingly high water permeability (P f ) characterizing the rat liver IMM. Immunoblotting, electron microscopy, and biophysical studies show that the largest mitochondria feature the highest AQP8 expression and IMM P f . AQP8 was also found in the mitochondria of other organs, whereas no other known aquaporins were seen. The osmotic water transport of liver IMM was partially inhibited by the aquaporin blocker Hg 2؉ , while the related activation energy remained low, suggesting the presence of a Hg 2؉ -insensitive facilitated pathway in addition to AQP8. It is suggested that AQP8-mediated water transport may be particularly important for rapid expansions of mitochondrial volume such as those occurring during active oxidative phosphorylation and those following apoptotic signals.Mitochondrial volume is of pivotal importance for the activity of the electron transport chain (1) and a control point of apoptosis (2). Changes in mitochondrial volume occur in many other physiological and patho-physiological conditions, including intracellular signal transduction, liver regeneration, ischemia/reperfusion-induced damage, and anoxia (3-5). Mitochondria are well behaved osmometers, and swelling and contraction of the mitochondrial matrix and related changes to mitochondrial morphology are the consequence of the water movement that osmotically accompanies the net transport of solutes into and out of the mitochondrion (6), respectively. Mitochondrial volume changes are modulated by the net movement of solutes including K ϩ and Ca 2ϩ ions across the IMM 1 (7,8). The inner mitochondrial membrane acts as a major barrier for the solutes and water moving between the cytoplasm and the mitochondrial matrix, the outer membrane being freely permeable to molecules of up to 1.5 kDa due to the presence of the exceedingly large pores formed by VDAC, the voltage-dependent anion channel (9). However, although a number of IMM transport systems have been cloned and characterized for their ability to transport solutes across the IMM (10), the molecular pathway for the movement of water remains obscure. Important clues for understanding the molecular bases of the mitochondrial osmotic properties were recently provided by the identification of an aquaporin water channel (11), AQP8, in rat hepatocyte mitochondria (12). AQP8 was also found in intracellular vesicles that are shuttled to the hepatocyte apical membrane under choleretic stimuli such as those brought about by glucagon (13). This led us to hyp...

Cytoprotective effects of growth factors: BDNF more potent than GDNF in an organotypic culture model of Parkinson's disease

“…These results indicate that mitochondria may contain an authentic pool of AQP9. The presence of mitochondrial expression of aquaporins is in line with previous findings, which have demonstrated expression of AQP8 in the inner mitochondrial membrane (279,280). This pool, however, has not shown a functional significance, as measured by water and glycerol permeability (281).…”

Specific Aquaporins Facilitate the Diffusion of Hydrogen Peroxide across Membranes

“…In mammals, AQP8 is present in the plasma membrane (51) and has recently been localized to the inner mitochondrial membrane (26). AQP8 may have a function in releasing H 2 O 2 from the mitochondrial matrix in situations when the electron transport chain is highly reduced, conditions known to generate ROS (1).…”

“…All data presented are averages of at least 12 trace recordings. The rate constant of the decrease of scattered light intensity is proportional to the water permeability coefficient (25,26). Rate constants were calculated by fitting the curves using non-linear regression as described earlier (27).…”

Lipopolysaccharide impairs hepatocyte ureagenesis from ammonia: Involvement of mitochondrial aquaporin‐8

“…In hepatocytes, a non-glycosylated 28 kDa form of AQP8 is present at the inner mitochondrial membranes (IMM) [13,14]. The expression of mitochondrial AQP8 (mtAQP8) seems to be greater in the periportal area of the hepatic lobule [13,14]. There is experimental evidence suggesting that mtAQP8 facilitates the ammonia transport across the IMM [15][16][17].…”

“…Aquaporin-8 (AQP8) is a member of a family of homologous membrane channel proteins demonstrated to facilitate the diffusional transport of ammonia [9][10][11][12]. In hepatocytes, a non-glycosylated 28 kDa form of AQP8 is present at the inner mitochondrial membranes (IMM) [13,14]. The expression of mitochondrial AQP8 (mtAQP8) seems to be greater in the periportal area of the hepatic lobule [13,14].…”