Bcl-2 and tBid proteins counter-regulate mitochondrial potassium transport

• Published in: Biochimica et biophysica acta 2003-04, Vol.1604 (1), p.1-5
• Main Authors: Eliseev, Roman A., Salter, Jason D., Gunter, Karlene K., Gunter, Thomas E.
• Format: Article
• Language: English
• Subjects: Apoptosis; bcl-2; BH3 Interacting Domain Death Agonist Protein; Carrier Proteins - physiology; Cytochrome c; Humans; Ion Transport; Mitochondria - metabolism; Mitochondrion; Potassium - metabolism; Potassium transport; Proto-Oncogene Proteins c-bcl-2 - physiology; tBid
• ISSN: 0005-2728; 0006-3002; 1879-2650
• DOI: 10.1016/S0005-2728(03)00005-7

The mechanism of cytochrome c release from mitochondria in apoptosis remains obscure, although it is known to be regulated by bcl-2 family proteins. Here we describe a set of novel apoptotic phenomena—stimulation of the mitochondrial potassium uptake preceding cytochrome c release and regulation of such potassium uptake by bcl-2 family proteins. As a result of increased potassium uptake, mitochondria undergo moderate swelling sufficient to release cytochrome c. Overexpression of bcl-2 protein prevented the mitochondrial potassium uptake as well as cytochrome c release in apoptosis. Bcl-2 was found to upregulate the mitochondrial potassium efflux mechanism—the K/H exchanger. Specific activation of the mitochondrial K-uniporter led to cytochrome c release, which was inhibited by bcl-2. tBid had an opposite effect—it stimulated mitochondrial potassium uptake resulting in cytochrome c release. The described counter-regulation of mitochondrial potassium transport by bcl-2 and Bid suggests a novel view of a mechanism of cytochrome c release from mitochondria in apoptosis.