Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41598-018-20856-6
Keywords
-
Categories
Funding
- NIH intramural programs of the NIDDK [1ZIADK075042, 1ZIADK060004-15]
- NHBLI [1ZIAHL006153]
- NCI [1ZIABC010763-11]
- Baltimore PKD Core Center [P30DK090868]
- NIH intramural core (NHLBI Flow Cytometry)
- NIH intramural core (NHLBI Light Microscopy)
- NIH intramural core (NIDDK Advanced Mass Spectrometry)
- NIH intramural core (NHLBI Electron Microscopy)
- NIH intramural core (NIDDK Advanced Light Microscopy and Image Analysis)
- Grants-in-Aid for Scientific Research [15K10632] Funding Source: KAKEN
Ask authors/readers for more resources
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(ko/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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available