Examining the role of defective oxidative phosphorylation in the normal and diseased prostate

NIH RePORTER · NIH · F31 · $38,608 · view on reporter.nih.gov ↗

Abstract

ABSTRACT Lower urinary tract symptoms (LUTS) are a significant burden to aging men and are often as a result of benign prostatic hyperplasia (BPH). While BPH/LUTS is not commonly fatal with proper medical intervention, it does cause a significant reduction in quality of life for many men as they age. Furthermore, BPH/LUTS increases risk of mortality and results in billions of dollars in healthcare costs annually. There is currently a subset of BPH/LUTS patients that fail FDA-approved treatments (α-blockers, 5ARI), and these patients have been shown to have increased prostatic fibrosis. There is no FDA-approved medication targeting fibrosis or the aging process in BPH/LUTS, even though aging is the greatest risk factor. This proposal aims to develop a better understanding about the role of aging, fibrosis, and mitochondrial dysfunction in BPH/LUTS. Mitochondrial dysfunction is a hallmark of both aging and fibrosis and has not been thoroughly studied in relation to BPH/LUTS. Preliminary data suggests that oxidative phosphorylation (OXPHOS) is a mitochondrial pathway contributing to cellular dysfunction in BPH/LUTS. Aim 1 of this proposal intends to investigate the connection between OXPHOS disruption and lower urinary tract dysfunction (LUTD) in a novel mouse model. Aim 2 of this proposal will investigate the connection between OXPHOS disruption and pathways associated with fibrosis, using genetic loss-of-function cell line models. Finally, Aim 3 will work to identify a new pathway of interest for treatment, using oleic acid as a mitochondrial metabolism modulator. Collectively, these aims will improve our overall understanding of the processes underlying BPH/LUTS, with a special focus on aging, mitochondrial dysfunction, and fibrosis. This proposal hopes to provide translational outcomes that can eventually improve patient care and treatment options.

Key facts

NIH application ID
10816415
Project number
5F31DK136335-02
Recipient
UNIVERSITY OF WISCONSIN-MADISON
Principal Investigator
Alexis Elizabeth Adrian
Activity code
F31
Funding institute
NIH
Fiscal year
2024
Award amount
$38,608
Award type
5
Project period
2023-04-01 → 2026-03-31