title: Aquaporin-assisted and ER-mediated mitochondrial fission: a hypothesis.
abstract: It is well established that the status of the endoplasmic reticulum (ER) and mitochondria, and the interactions between them, is critical to numerous cellular functions including apoptosis. Mitochondrial dynamics is greatly influenced by cell stress, and recent studies implicate ER in mitochondrial fission. Although a number of proteins have been identified to participate in ER-induced mitochondrial fission, the molecular mechanism of the process is little understood. In the current study, we confirm the involvement of ER in mitochondrial fission and hypothesize the involvement of water channels or aquaporins (AQP) in the process. Previous studies demonstrate the presence of AQP both in the ER and mitochondrial membranes. Mitochondrial swelling has been observed following mitochondrial calcium overload, and studies report that chelation of cytosolic calcium induces extensive mitochondrial division at ER contact sites. Based on this information, the involvement of ER in mitochondrial division, possibly via water channels, is hypothesized. Utilizing a multi-faceted imaging approach consisting of atomic force microscopy on aldehyde-fixed and semi-dry cells, transmission electron microscopy, and immunofluorescence microscopy on live cells, the physical interactions between the two organelles are demonstrated. Mitochondrial fission following ER stress was abrogated with exposure of cells to the AQP inhibitor mercuric chloride, suggesting the involvement of AQP(s) especially AQP8 and AQP9 known to be present in the mitochondrial membrane, in mitochondrial fission.
authors: Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
authors: Jin-Sook
authors: JS
authors: Lee
authors: Xia
authors: X
authors: Hou
authors: Nicole
authors: N
authors: Bishop
authors: Sunxi
authors: S
authors: Wang
authors: Amanda
authors: A
authors: Flack
authors: Won Jin
authors: WJ
authors: Cho
authors: Xuequn
authors: X
authors: Chen
authors: Guangzhao
authors: G
authors: Mao
authors: Douglas J
authors: DJ
authors: Taatjes
authors: Fei
authors: F
authors: Sun
authors: Kezhong
authors: K
authors: Zhang
authors: Bhanu P
authors: BP
authors: Jena
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000378:metabolism* / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000502:physiology*; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D063154:Mitochondrial Dynamics / Q000187:drug effects / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000378:metabolism; D046790:Pancreas, Exocrine / Q000166:cytology / Q000648:ultrastructure; D010195:Pancreatitis / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020346:Aquaporins