Bax mediates cytochrome c release and mitochondrial depolarization in lymphocytes by interacting with and inhibiting the mitochondrial potassium channel Kv1.3.
Does the mitochondrial potassium channel Kv1.3 mediate Bax-induced apoptosis in lymphocytes?
The mitochondrial potassium channel Kv1.3 mediates Bax-induced apoptosis in lymphocytes, suggesting a novel mechanism for cytochrome c release and mitochondrial depolarization.
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.
Szabó et al. (Thu,) conducted a other in Apoptosis in lymphocytes. Bax and Kv1.3 modulation vs. Kv1.3-deficient cells or control vectors was evaluated on Apoptosis (DNA fragmentation, cytochrome c release, mitochondrial depolarization). Bax mediates cytochrome c release and mitochondrial depolarization in lymphocytes by interacting with and inhibiting the mitochondrial potassium channel Kv1.3.