title: Mitochondrial disease and endocrine dysfunction.
abstract: Mitochondria are critical organelles for endocrine health; steroid hormone biosynthesis occurs in these organelles and they provide energy in the form of ATP for hormone production and trafficking. Mitochondrial diseases are multisystem disorders that feature defective oxidative phosphorylation, and are characterized by enormous clinical, biochemical and genetic heterogeneity. To date, mitochondrial diseases have been found to result from >250 monogenic defects encoded across two genomes: the nuclear genome and the ancient circular mitochondrial genome located within mitochondria themselves. Endocrine dysfunction is often observed in genetic mitochondrial diseases and reflects decreased intracellular production or extracellular secretion of hormones. Diabetes mellitus is the most frequently described endocrine disturbance in patients with inherited mitochondrial diseases, but other endocrine manifestations in these patients can include growth hormone deficiency, hypogonadism, adrenal dysfunction, hypoparathyroidism and thyroid disease. Although mitochondrial endocrine dysfunction frequently occurs in the context of multisystem disease, some mitochondrial disorders are characterized by isolated endocrine involvement. Furthermore, additional monogenic mitochondrial endocrine diseases are anticipated to be revealed by the application of genome-wide next-generation sequencing approaches in the future. Understanding the mitochondrial basis of endocrine disturbance is key to developing innovative therapies for patients with mitochondrial diseases.
authors.affiliation: Department of Paediatrics, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong, China.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Chow
authors.affiliation: Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Joyeeta
authors.initials: J
authors.lastname: Rahman
authors.affiliation: Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Achermann
authors.affiliation: Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.|Endocrinology Unit, Great Ormond Street Hospital NHS Foundation Trust, Great Ormond Street, London WC1N 3JH, UK.
authors.forename: Mehul T
authors.initials: MT
authors.lastname: Dattani
authors.affiliation: Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.|Metabolic Unit, Great Ormond Street Hospital NHS Foundation Trust, Great Ormond Street, London WC1N 3JH, UK.
authors.forename: Shamima
authors.initials: S
authors.lastname: Rahman
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004700:Endocrine System Diseases / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D013959:Thyroid Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial