THADA regulates the organismal balance between energy storage and heat production
| العنوان: | THADA regulates the organismal balance between energy storage and heat production |
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| المؤلفون: | Aurelio A. Teleman, Markus Jabs, Martin Frejno, Katrin Strassburger, Markus Ralser, Matilda Males, Bart P. Braeckman, Alexandra Moraru, Gulcin Cakan-Akdogan, Sandra Mueller, Michael Muelleder |
| المصدر: | DEVELOPMENTAL CELL Developmental Cell |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, obesity, HOMEOSTASIS, Hot Temperature, Mutant, Regulator, Endoplasmic Reticulum, medicine.disease_cause, CA2+-ATPASE, Gene Knockout Techniques, Drosophila Proteins, Conserved Sequence, Mutation, Effector, Ecology, INSULIN SENSITIVITY, thermogenesis, ASSOCIATION, Neoplasm Proteins, Cell biology, DROSOPHILA, Drosophila melanogaster, sarcolipin, OBESITY, Female, Drosophila, type 2 diabetes, Protein Binding, medicine.medical_specialty, endocrine system, SERCA, SUSCEPTIBILITY LOCI, PROTEINS, THERMOGENESIS, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Energy storage, Sarcoplasmic Reticulum Calcium-Transporting ATPases, MECHANISMS, 03 medical and health sciences, Internal medicine, medicine, Animals, Humans, Production (economics), development, Molecular Biology, book, calcium, Developmental cell, Correction, Biology and Life Sciences, Cell Biology, biology.organism_classification, Endocrinology, 030104 developmental biology, Balance (accounting), book.journal, Carrier Proteins, Energy Metabolism, Developmental biology, metabolism, HeLa Cells, Developmental Biology |
| الوصف: | Summary Human susceptibility to obesity is mainly genetic, yet the underlying evolutionary drivers causing variation from person to person are not clear. One theory rationalizes that populations that have adapted to warmer climates have reduced their metabolic rates, thereby increasing their propensity to store energy. We uncover here the function of a gene that supports this theory. THADA is one of the genes most strongly selected during evolution as humans settled in different climates. We report here that THADA knockout flies are obese, hyperphagic, have reduced energy production, and are sensitive to the cold. THADA binds the sarco/ER Ca2+ ATPase (SERCA) and acts on it as an uncoupler. Reducing SERCA activity in THADA mutant flies rescues their obesity, pinpointing SERCA as a key effector of THADA function. In sum, this identifies THADA as a regulator of the balance between energy consumption and energy storage, which was selected during human evolution. Highlights • Drosophila knockouts of the conserved gene THADA are obese and hyperphagic • THADA knockouts produce less heat and are cold sensitive • THADA binds SERCA and uncouples its ATP hydrolysis from Ca2+ pumping • Reducing SERCA activity rescues the THADA loss-of-function phenotypes One theory for variable human susceptibility to obesity is altered metabolic rates due to adaptation to warmer climates. Moraru et al. examine the function of THADA, a positively selected gene in human evolution associated with type 2 diabetes, in Drosophila and show that THADA modulates, via calcium signaling, energy storage and thermogenesis balance. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1534-5807 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8e373d3c530cc7e73ab01dff743f90a https://hdl.handle.net/1854/LU-8517675 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e8e373d3c530cc7e73ab01dff743f90a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15345807 |
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