Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease
Abstract
Renal epithelial cells (RECs) contain abundant mitochondria that are essential to support renal reabsorption of electrolytes, glucose, and amino acids. However, it remains poorly understood how mitochondrial metabolism is coordinated with kidney reabsorptive functions. Here we show that deletion of estrogen-related receptor gamma (ERRγ) in RECs results in severe renal mitochondrial and reabsorptive dysfunction with fluid-filled cysts. ERRγ directly regulates mitochondrial metabolism and cooperates in regulating renal reabsorption genes with hepatic nuclear factor 1 beta (HNF1β), mutations of which cause strikingly similar renal dysfunction and cysts in animals and humans. These findings reveal a role for ERRγ in simultaneously coordinating a transcriptional program of renal energy-generating mitochondrial and energy-consuming reabsorptive functions relevant to kidney disease.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 07, 2018
- Source ID
- 10.1073/pnas.1804965115
Entities
People
- Amanda L. Allred
- Benjamin J. Wilkins
- Caitlin Mcdonald
- Chengxiang Qiu
- Grant D Barish
- Jian Liu
- Juanjuan Zhao
- Katalin Susztak
- Katherine Lupino
- Liming Pei
- Yasuhiro Omura
Organizations
- Children's Hospital of Philadelphia
- National Institutes of Health
- Northwestern University
- United States Department of Defense
- University of Pennsylvania