The complex crosstalk between mitochondria and the nucleus: What goes in between?

Mitochondria are critical metabolic hubs in which catabolic and anabolic cellular processes converge and are integrated. To perform their function, mitochondria also need to respond to signals that monitor their function and send continuous feedback to the nucleus and other organelles to trigger the required expression programs (for example, stabilization of hypoxia-inducible factor 1-α). Unsurprisingly, mitochondrial dysfunction results in wide range of disorders. Understanding how cells adapt to changes in mitochondrial function is critical for the evaluation of mitochondrial disorders and the development of potential treatments. Each type of mitochondrial dysfunction results in a unique transcriptional response. Here we review the role of nuclear-encoded factors in the response to changes in mitochondrial function and discuss their relevance to metabolic homeostasis, outlining the diverse and complex ways in which nuclei adapt to maintain mitochondrial homeostasis. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies.