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Mitochondrial Endocrinology – Mitochondria As Key to Hormones and Metabolism

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Mitochondrial Endocrinology – Mitochondria As Key to Hormones and Metabolism Molecular and Cellular Endocrinology 379 (2013) 1–1 Contents lists available at SciVerse ScienceDirect Molecular and Cellular Endocrinology journal homepage: www.elsevier.com/locate/mce Editorial Mitochondrial endocrinology – Mitochondria as key to hormones and metabolism Mitochondria are puzzling organelles, which provided exciting insights into cellular function as recently reviewed by one of its pio- neers (Schatz, 2013). But still many of their features in (patho)phys- iologic conditions and in disease states are not fully understood. Despite their critical role for all animal organisms, their impact on several endocrine and metabolic functions is of specific importance. Not do they only host several metabolic pathways, including the tri- carboxylic (Krebs) cycle and b-oxidation, mitochondria are also the key to lipid, cholesterol and hormone biosynthesis as well as main- tain the cytosolic free calcium concentration. Free cytosolic calcium in turn serves as cellular signal in divergent pathways, such as hor- monal signaling (Stark and Roden, 2007). On the other hand, certain hormones exert their central endocrine action directly or indirectly via affecting mitochondrial function in various tissues and diver- gent cell-types. The growing interest of current research in this field stimulated us to compile contributions to hot topics addressing aspects of so- called mitochondrial endocrinology (Wrutniak-Cabello et al., 2002). First, studies of humans with genetically confirmed mito- chondrial abnormalities, commonly called mitochondrial diseases, can serve as nature’s proof of the importance of mitochondria also for endocrine function, which is not limited to the pancreatic ß cell by causing mitochondrial diabetes. These inborn diseases might therefore help to better understand abnormal mitochondrial func- References tion in humans. Reviewing hormone synthesis, with a focus on ste- roid hormones and vitamin D, and hormone action, particularly Schatz, G., 2013. Getting mitochondria to center stage. Biochem. Biophys. Res. Commun. 434, 407–410. describing the role of thyroid hormones for mitochondrial biogene- Stark, R., Roden, M., 2007. ESCI Award 2006. Mitochondrial function and endocrine sis, is followed by a summary on the complex role of mitochondria diseases. Eur. J. Clin. Invest. 37, 236–248. for sex hormone synthesis but also steroid-independent effects on Wrutniak-Cabello, C., Casas, F., Grandemange, S., Seyer, P., Busson, M., Carazo, A., Cabello, G., 2002. Study of thyroid hormone action on mitochondria opens up a mammalian reproduction. Second, seminal studies in the field of new field of research: mitochondrial endocrinology. Curr. Opin. Endocrinol. metabolism stimulated mitochondrial endocrinology over the last Diab. 9, 387–392. decade by shedding more light on regulation of energy homeostasis Szendroedi, J., Phielix, E., Roden, M., 2011. The role of mitochondria in insulin resistance and type 2 diabetes mellitus. Nat. Rev. Endocrinol. 8, 92–103. or precisely the balance between energy intake and expenditure for alterations associated with ageing, obesity and diabetes mellitus. A Michael Roden relevant proportion of these new insights resulted from the devel- Institute for Clinical Diabetology, opment of novel invasive and noninvasive technologies allowing German Diabetes Center, assessing various aspects of mitochondria, also in humans (Szendr- Leibniz Center for Diabetes Research, Düsseldorf, Germany oedi et al., 2011). The findings range from age-dependent altera- tions over dynamic changes in mitochondrial function in skeletal Unic. Clinics of Endocrinology and Diabetology, muscle and liver to the chameleon-like behavior of adipose tissue Heinrich-Heine University, Düsseldorf, Germany to adapt heat production and subtle regulation of ß-cell function. E-mail address: [email protected] While the present selection cannot be comprehensive, it was designed to briefly summarize hot topics in mitochondrial endocri- Available online 20 June 2013 nology as of 2013. I would like to thank all the contributors for their excellent cooperation, the team of Mol Cell Endocrinol for their support and my Assistant Mrs. Beate Stodieck for her help with this task. 0303-7207/$ - see front matter Ó 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.mce.2013.06.017 Molecular and Cellular Endocrinology 379 (2013) 2–11 Contents lists available at ScienceDirect Molecular and Cellular Endocrinology journal homepage: www.elsevier.com/locate/mce Review Endocrine disorders in mitochondrial disease q a, b a a, Andrew M. Schaefer ⇑, Mark Walker , Douglass M. Turnbull , Robert W. Taylor ⇑ a Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK b Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK article info abstract Article history: Endocrine dysfunction in mitochondrial disease is commonplace, but predominantly restricted to disease Available online 13 June 2013 of the endocrine pancreas resulting in diabetes mellitus. Other endocrine manifestations occur, but are relatively rare by comparison. In mitochondrial disease, neuromuscular symptoms often dominate the Keywords: clinical phenotype, but it is of paramount importance to appreciate the multi-system nature of the dis- Mitochondrial disease ease, of which endocrine dysfunction may be a part. The numerous phenotypes attributable to pathogenic Endocrine mutations in both the mitochondrial (mtDNA) and nuclear DNA creates a complex and heterogeneous mtDNA catalogue of disease which can be difficult to navigate for novices and experts alike. In this article we pro- Diabetes vide an overview of the endocrine disorders associated with mitochondrial disease, the way in which the m.3243A > G underlying mitochondrial disorder influences the clinical presentation, and how these factors influence subsequent management. Ó 2013 The Authors. Published by Elsevier Ireland Ltd. All rights reserved. Contents 1. Introduction ........................................................................................................... 3 2. Mitochondrial biochemistry and genetics. ........................................................................ 3 3. Investigation of mitochondrial disease . ........................................................................ 3 4. Diabetes mellitus . ........................................................................................... 4 5. Mitochondrial diabetes . ........................................................................................... 4 5.1. Pattern recognition . .............................................................................. 4 5.2. Age-at-onset . ................................................................................................. 5 5.3. Insulin requirements. .............................................................................. 5 5.4. Body Mass Index (BMI) . .............................................................................. 5 5.5. End organ disease ................................................................................................. 5 5.6. Pancreatic pathology. .............................................................................. 6 5.7. Diabetes management. .............................................................................. 6 6. Hypoparathyroidism . ........................................................................................... 6 7. Hypothalamo-pituitary axis. ........................................................................................... 7 8. Growth hormone deficiency . ........................................................................................... 7 9. Hypogonadism . ........................................................................................... 7 10. Hypothyroidism . ........................................................................................... 7 11. Hypoadrenalism . ........................................................................................... 7 12. SIADH . ........................................................................................................... 7 13. Adipose tissue as an endocrine organ. ........................................................................ 7 14. Autoimmune endocrinopathy . ........................................................................................... 8 15. Conclusion . ........................................................................................................... 8 Acknowledgments . ........................................................................................... 8 References . ........................................................................................................... 8 q This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non- commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. Corresponding authors. Address: Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, The Medical School, Newcastle University, ⇑ Framlington Place, Newcastle upon Tyne NE2 4HH, UK. Tel.: +44 1912223685. E-mail addresses: [email protected] (A.M. Schaefer), [email protected] (R.W. Taylor). 0303-7207/$ - see front matter Ó 2013 The Authors. Published by Elsevier Ireland Ltd. All
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