title: Mitochondrial potassium channel Kv1.3 mediates Bax-induced apoptosis in lymphocytes.
abstract: The potassium channel Kv1.3 has recently been located to the inner mitochondrial membrane of lymphocytes. Here, we show that mouse and human cells either genetically deficient in Kv1.3 or transfected with siRNA to suppress Kv1.3-expression resisted apoptosis induced by several stimuli, including Bax over-expression [corrected]. Retransfection of either Kv1.3 or a mitochondrial-targeted Kv1.3 restored cell death . Bax interacted with and functionally inhibited mitochondrial Kv1.3. Incubation of isolated Kv1.3-positive mitochondria with recombinant Bax, t-Bid, or toxins that bind to and inhibit Kv1.3 successively triggered hyperpolarization, formation of reactive oxygen species, release of cytochrome c, and marked depolarization. Kv1.3-deficient mitochondria were resistant to Bax, t-Bid, and the toxins. Mutation of Bax at K128, which corresponds to a conserved lysine in Kv1.3-inhibiting toxins, abrogated its effects on both Kv1.3 and mitochondria. These findings suggest that Bax mediates cytochrome c release and mitochondrial depolarization in lymphocytes, at least in part, via its interaction with mitochondrial Kv1.3.
authors.affiliation: Department of Biology, University of Padova, Viale G. Colombo 3, 35121 Padua, Italy.
authors.forename: Ildikò
authors.initials: I
authors.lastname: Szabó
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bock
authors.forename: Heike
authors.initials: H
authors.lastname: Grassmé
authors.forename: Matthias
authors.initials: M
authors.lastname: Soddemann
authors.forename: Barbara
authors.initials: B
authors.lastname: Wilker
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Mario
authors.initials: M
authors.lastname: Zoratti
authors.forename: Erich
authors.initials: E
authors.lastname: Gulbins
mesh_terms: D000818:Animals; D017209:Apoptosis; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D051664:Kv1.3 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D034741:RNA, Small Interfering / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D051664:Kv1.3 Potassium Channel; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c