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

SUBMITTER: Szabo I 

PROVIDER: S-EPMC2567458 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature