Format

Send to

Choose Destination
Sci Rep. 2018 Feb 9;8(1):2743. doi: 10.1038/s41598-018-20856-6.

A cleavage product of Polycystin-1 is a mitochondrial matrix protein that affects mitochondria morphology and function when heterologously expressed.

Author information

1
Kidney Disease Branch; National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health (NIH), Bethesda, MD, USA.
2
Laboratory of Molecular Genetics; National Heart, Lung and Blood Institute, NIH, Bethesda, MD, USA.
3
Division of Nephrology and Endocrinology and the Division of CKD Pathophysiology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
4
Laboratory of Cell and Molecular Biology; National Institute of Diabetes and Digestive and Kidney Disease, NIH, Bethesda, MD, USA.
5
Center for Cell-Based Therapy, National Cancer Institute, NIH, Bethesda, MD, USA.
6
Department of Medicine, Division of Nephrology, University of Maryland School of Medicine, Baltimore, MD, USA.
7
Department of Urology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
8
Kidney Disease Branch; National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health (NIH), Bethesda, MD, USA. luis.menezes@nih.gov.
9
Kidney Disease Branch; National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health (NIH), Bethesda, MD, USA. germinogg@mail.nih.gov.

Abstract

Recent studies have reported intrinsic metabolic reprogramming in Pkd1 knock-out cells, implicating dysregulated cellular metabolism in the pathogenesis of polycystic kidney disease. However, the exact nature of the metabolic changes and their underlying cause remains controversial. We show herein that Pkd1 k o /ko renal epithelial cells have impaired fatty acid utilization, abnormal mitochondrial morphology and function, and that mitochondria in kidneys of ADPKD patients have morphological alterations. We further show that a C-terminal cleavage product of polycystin-1 (CTT) translocates to the mitochondria matrix and that expression of CTT in Pkd1 ko/ko cells rescues some of the mitochondrial phenotypes. Using Drosophila to model in vivo effects, we find that transgenic expression of mouse CTT results in decreased viability and exercise endurance but increased CO2 production, consistent with altered mitochondrial function. Our results suggest that PC1 may play a direct role in regulating mitochondrial function and cellular metabolism and provide a framework to understand how impaired mitochondrial function could be linked to the regulation of tubular diameter in both physiological and pathological conditions.

PMID:
29426897
PMCID:
PMC5807443
DOI:
10.1038/s41598-018-20856-6
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center