Nitric oxide signaling regulates mitochondrial number and function.

Abstract

Obesity affects many millions of children and adults worldwide and poses a major health problem. Weight gain results when energy intake exceeds energy expenditure. Energy can be dissipated in the form of work or heat. In order to combat obesity and associated disease, including diabetes, heart attack, and stroke, understanding how our body regulates energy balance will be of fundamental importance. Recent findings have revealed that the brain regulates energy expenditure. Environmental cues, such as cold, exercise, and food-intake signal the sympathetic nervous system to trigger the release of the hormone, noradrenaline, which in turn innervates brown adipose tissue (BAT) by binding to the -adrenergic receptor (reviewed in Lowell and Spiegelman1). BAT is the major site of adaptive thermogenesis, which protects the body from cold and controls the response to changes in diet. -adrenergic receptor stimulation then leads to mitochondrial biogenesis (mitochondrial proliferation and activation). The mitochondrion can be viewed as a cellular furnace where fatty acids and glucose are oxidized, and energy is stored as ATP or wasted as heat, thus regulating cellular energy balance. The exact pathways that lead to mitochondrial proliferation in response to -adrenergic receptor signaling in BAT are not entirely understood. Clues have emerged indicating that transcriptional control is implicated in this process.2,3,4,5,6 Now Nisoli et al.7 have made the intriguing discovery that the gas nitric oxide (NO) links -adrenergic receptor signaling with mitochondrial biogenesis by increasing the activity of a master transcriptional regulator of the mitochondrial biogenesis program. Here we will highlight the observations made by Nisoli and colleagues and speculate on their potential implications for the study of energy metabolism, aging, and cell death.