Asset Details
Do you wish to reserve the book?
NCLX prevents cell death during adrenergic activation of the brown adipose tissue
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
NCLX prevents cell death during adrenergic activation of the brown adipose tissue
Do you wish to request the book?
NCLX prevents cell death during adrenergic activation of the brown adipose tissue
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
NCLX prevents cell death during adrenergic activation of the brown adipose tissue
2020
Overview
A sharp increase in mitochondrial Ca
2+
marks the activation of brown adipose tissue (BAT) thermogenesis, yet the mechanisms preventing Ca
2+
deleterious effects are poorly understood. Here, we show that adrenergic stimulation of BAT activates a PKA-dependent mitochondrial Ca
2+
extrusion via the mitochondrial Na
+
/Ca
2+
exchanger, NCLX. Adrenergic stimulation of NCLX-null brown adipocytes (BA) induces a profound mitochondrial Ca
2+
overload and impaired uncoupled respiration. Core body temperature, PET imaging of glucose uptake and VO
2
measurements confirm a thermogenic defect in NCLX-null mice. We show that Ca
2+
overload induced by adrenergic stimulation of NCLX-null BAT, triggers the mitochondrial permeability transition pore (mPTP) opening, leading to a remarkable mitochondrial swelling and cell death. Treatment with mPTP inhibitors rescue mitochondrial function and thermogenesis in NCLX-null BAT, while calcium overload persists. Our findings identify a key pathway through which BA evade apoptosis during adrenergic stimulation of uncoupling. NCLX deletion transforms the adrenergic pathway responsible for thermogenesis activation into a death pathway.
Brown adipose tissue activation of thermogenesis is accompanied by a sequence of events commonly associated with apoptosis, however they evade cell death. Assali et al. show that NCLX prevents mitochondrial calcium overload and apoptosis. Deletion of NCLX, converts a thermogenic signal into a death pathway.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/51
/ 13/95
/ 14/19
/ 14/28
/ 14/34
/ 14/35
/ 14/63
/ 59/78
/ 64
/ 64/60
/ 82/80
/ 96/1
/ 96/2
/ Adipocytes, Brown - cytology
/ Adipocytes, Brown - drug effects
/ Adipocytes, Brown - pathology
/ Adipose Tissue, Brown - cytology
/ Adipose Tissue, Brown - metabolism
/ Adrenergic Agents - pharmacology
/ Animals
/ Calcium
/ Cold Temperature - adverse effects
/ Deletion
/ Energy Metabolism - drug effects
/ Energy Metabolism - physiology
/ Female
/ Humanities and Social Sciences
/ Male
/ Mice
/ Mitochondrial Membrane Transport Proteins - antagonists & inhibitors
/ Mitochondrial Membrane Transport Proteins - metabolism
/ Mitochondrial Permeability Transition Pore
/ Science
/ Sodium-Calcium Exchanger - genetics
/ Sodium-Calcium Exchanger - metabolism
