Spatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity

Güneş Parlakgül, Song Pang, Leonardo L. Artico, Nina Min, Erika Cagampan, Reyna Villa, Renata L. S. Goncalves, Grace Yankun Lee, C. Shan Xu, Gökhan S. Hotamışlıgil () and Ana Paula Arruda ()
Additional contact information
Güneş Parlakgül: Harvard T.H. Chan School of Public Health
Song Pang: HHMI Janelia Research Campus
Leonardo L. Artico: University of California, Berkeley
Nina Min: Harvard T.H. Chan School of Public Health
Erika Cagampan: Harvard T.H. Chan School of Public Health
Reyna Villa: University of California, Berkeley
Renata L. S. Goncalves: Harvard T.H. Chan School of Public Health
Grace Yankun Lee: Harvard T.H. Chan School of Public Health
C. Shan Xu: HHMI Janelia Research Campus
Gökhan S. Hotamışlıgil: Harvard T.H. Chan School of Public Health
Ana Paula Arruda: University of California, Berkeley

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract The hepatocytes within the liver present an immense capacity to adapt to changes in nutrient availability. Here, by using high resolution volume electron microscopy, we map how hepatic subcellular spatial organization is regulated during nutritional fluctuations and as a function of liver zonation. We identify that fasting leads to remodeling of endoplasmic reticulum (ER) architecture in hepatocytes, characterized by the induction of single rough ER sheet around the mitochondria, which becomes larger and flatter. These alterations are enriched in periportal and mid-lobular hepatocytes but not in pericentral hepatocytes. Gain- and loss-of-function in vivo models demonstrate that the Ribosome receptor binding protein1 (RRBP1) is required to enable fasting-induced ER sheet-mitochondria interactions and to regulate hepatic fatty acid oxidation. Endogenous RRBP1 is enriched around periportal and mid-lobular regions of the liver. In obesity, ER-mitochondria interactions are distinct and fasting fails to induce rough ER sheet-mitochondrion interactions. These findings illustrate the importance of a regulated molecular architecture for hepatocyte metabolic flexibility.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-48272-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48272-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-48272-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().