Mitochondrial biogenesis: Which part of “NO” do we understand?

A recent paper by Nisoli et al. [1] provides the first evidence that elevated levels of nitric oxide (NO) stimulate mitochondrial biogenesis in a number of cell lines via a soluble guanylate-cyclase-dependent signaling pathway that activates PGC1alpha (peroxisome proliferator-activated receptor gamma coactivator-1alpha), a master regulator of mitochondrial content. These results raise intriguing possibilities for a role of NO in modulating mitochondrial content in response to physiological stimuli such as exercise or cold exposure. However, whether this signaling cascade represents a widespread mechanism by which mammalian tissues regulate mitochondrial content, and how it might integrate with other pathways that control PGC1alpha expression, remain unclear.