Chronic enrichment of hepatic ER-mitochondria contact sites leads to calcium dependent mitochondrial dysfunction in obesity

DSpace/Manakin Repository

Chronic enrichment of hepatic ER-mitochondria contact sites leads to calcium dependent mitochondrial dysfunction in obesity

Citable link to this page

 

 
Title: Chronic enrichment of hepatic ER-mitochondria contact sites leads to calcium dependent mitochondrial dysfunction in obesity
Author: Arruda, Ana Paula; Pers, Benedicte Mengel; Parlakgül, Güneş; Güney, Ekin; Inouye, Karen; Hotamisligil, Gökhan S.

Note: Order does not necessarily reflect citation order of authors.

Citation: Arruda, Ana Paula, Benedicte Mengel Pers, Güneş Parlakgül, Ekin Güney, Karen Inouye, and Gökhan S. Hotamisligil. 2015. “Chronic enrichment of hepatic ER-mitochondria contact sites leads to calcium dependent mitochondrial dysfunction in obesity.” Nature medicine 20 (12): 1427-1435. doi:10.1038/nm.3735. http://dx.doi.org/10.1038/nm.3735.
Full Text & Related Files:
Abstract: Proper function of the endoplasmic reticulum (ER) and mitochondria is critical for cellular homeostasis, and dysfunction at either site has been linked to pathophysiological states including metabolic diseases. Although ER and mitochondria play distinct cellular roles, these organelles also form physical interactions at sites defined as mitochondria associated ER-membranes (MAMs), which are essential for Ca2+, lipid and metabolite exchange. Here we show that in the liver, obesity leads to a significant reorganization of MAMs resulting in mitochondrial Ca2+ overload, compromised mitochondrial oxidative capacity and augmented oxidative stress. Experimental induction of ER-mitochondria interactions results in oxidative stress and impaired metabolic homeostasis, while down-regulation of PACS-2 or IP3R1, proteins important for ER-mitochondria tethering and calcium transport respectively, improves mitochondrial oxidative capacity and insulin sensitivity in obese animals. These findings establish excessive ER-mitochondrial coupling as an essential component of organelle dysfunction in obesity, which may contribute to the development of metabolic pathologies such as insulin resistance.
Published Version: doi:10.1038/nm.3735
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412031/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:17295575
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters