Light-Regulated Transcription of a Mitochondrial-Targeted K Channel.

The inner membranes of mitochondria contain several types of K channels, which modulate the membrane potential of the organelle and contribute in this way to cytoprotection and the regulation of cell death. To better study the causal relationship between K channel activity and physiological changes, we developed an optogenetic platform for a light-triggered modulation of K conductance in mitochondria. By using the light-sensitive interaction between cryptochrome 2 and the regulatory protein CIB1, we can trigger the transcription of a small and highly selective K channel, which is in mammalian cells targeted into the inner membrane of mitochondria. After exposing cells to very low intensities (≤0.16 mW/mm) of blue light, the channel protein is detectable as an accumulation of its green fluorescent protein (GFP) tag in the mitochondria less than 1 h after stimulation. This system allows for an in vivo monitoring of crucial physiological parameters of mitochondria, showing that the presence of an active K channel causes a substantial depolarization compatible with the effect of an uncoupler. Elevated K conductance also results in a decrease in the Ca concentration in the mitochondria but has no impact on apoptosis.