Marathon runners should give NF-κB a hand. Bakkar et al. show that the transcription factor pushes muscles to make more mitochondria and to produce the type of fiber that tires slowly.
NF-κB has a split personality during muscle development and regeneration. On the one hand, it can be activated by the so-called classical pathway that prevents young muscle cells from differentiating. But NF-κB can also be regulated by an alternative pathway, which involves a distinct set of proteins, including IKKα and RelB. Researchers are just starting to investigate the alternative pathway's role in muscle. In a previous study, Bakkar et al. found that it spurs cultured muscle cells to generate mitochondria.
Now, the researchers gauged the alternative pathway's powers in vivo by analyzing mice that lacked IKKα or RelB. Muscles from the animals had fewer mitochondria than normal and showed signs of an energy shortage. What mitochondria they did contain were less efficient. Overexpressing IKKα had the opposite effect, boosting mitochondrial numbers and power output and inducing muscles to fashion more slow twitch fibers. Although weaker than fast twitch fibers, slow twitch fibers have more stamina and are critical for long-distance runners.
Bakkar et al. found that the alternative NF-κB pathway exerts its effects by activating PGC-1β, a master regulator of mitochondrial biogenesis and function. The researchers also discovered that mTOR, which responds to hormones, growth factors, and nutrient levels, activates the pathway. What triggers mTOR to flip on NF-κB and the alternative pathway remains unclear.
