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  • Review Article
  • Published:

Mitochondrial dynamics in the central regulation of metabolism

Nature Reviews Endocrinology volume 10, pages 650–658 (2014)Cite this article

Subjects

Key Points

  • Mitochondrial dynamics in hypothalamic neurons affect peripheral tissue function in metabolic disorders such as obesity

  • Activation of neuropeptide-Y-agouti-related-protein (NPY–AgRP) neurons mediates an orexigenic response, which promotes hunger, whereas activation of proopiomelanocortin (POMC) neurons results in an anorexigenic response that promotes appetite suppression

  • NPY–AgRP neurons and POMC neurons are components of the central melanocortin system and are activated via distinct signalling pathways, each of which is dependent on mitochondrial dynamics

  • Activation of NPY–AgRP neurons occurs through metabolism of fatty acids whereas activation of POMC neurons is dependent on glucose metabolism

  • The molecular regulators of mitochondrial fusion, Mfn1 and Mfn2, have distinct functions in specific cell types

  • Impairment of mitochondrial dynamics contributes to development of metabolic disorders, such as obesity and diabetes mellitus

Abstract

The ability of an organism to convert organic molecules from the environment into energy is essential for the development of cellular structures, cell differentiation and growth. Mitochondria have a fundamental role in regulating metabolic pathways, and tight control of mitochondrial functions and dynamics is critical to maintaining adequate energy balance. In complex organisms, such as mammals, it is also essential that the metabolic demands of various tissues are coordinated to ensure that the energy needs of the whole body are effectively met. Within the arcuate nucleus of the hypothalamus, the NPY–AgRP and POMC neurons have a crucial role in orchestrating the regulation of hunger and satiety. Emerging findings from animal studies have revealed an important function for mitochondrial dynamics within these two neuronal populations, which facilitates the correct adaptive responses of the whole body to changes in the metabolic milieu. The main proteins implicated in these studies are the mitofusins, Mfn1 and Mfn2, which are regulators of mitochondrial dynamics. In this Review, we provide an overview of the mechanisms by which mitochondria are involved in the central regulation of energy balance and discuss the implications of mitochondrial dysfunction for metabolic disorders.

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Figure 1: Melanocortin system in the arcuate nucleus of the hypothalamus.
Figure 2: Regulation of POMC and NPY–AgRP neuron activation.
Figure 3: Feeding states and mitochondrial dynamics in NPY–AgRP and POMC neurons.

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Authors and Affiliations

  1. Program in Integrative Cell Signalling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, SHM L-200, PO Box 208074, New Haven, 06520-8074, CT, USA

    Carole M. Nasrallah & Tamas L. Horvath

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  1. Carole M. Nasrallah
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C.M.N. and T.L.H contributed equally to researching data for the article, to discussions of the content, to writing of the article and to review and/or editing of the manuscript before submission.

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Correspondence to Tamas L. Horvath.

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Nasrallah, C., Horvath, T. Mitochondrial dynamics in the central regulation of metabolism. Nat Rev Endocrinol 10, 650–658 (2014). https://doi.org/10.1038/nrendo.2014.160

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