Faculty Collaboration Database

Sex Differences in Renal Mitochondrial Respiration and H2O2 Emission in Young Dahl Salt-Sensitive Rats. Function (Oxf) 2025 Oct 28;6(6)

Date

10/07/2025

Pubmed ID

41055389

Pubmed Central ID

PMC12560232

DOI

10.1093/function/zqaf045

Scopus ID

2-s2.0-105020316608 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

Sexual dimorphism profoundly influences physiology, disease susceptibility, and therapeutic responses, yet its effects on kidney mitochondrial function remain unclear. We hypothesized that sex differences in kidney mitochondrial function would parallel those in other organs, with females exhibiting greater oxidative capacity and lower oxidative stress. To test this, we measured oxidative phosphorylation (OXPHOS) kinetics and hydrogen peroxide (H2O2) emission in cortical and outer medullary (OM) mitochondria isolated from young male and female Dahl salt-sensitive (SS) rats maintained on a low-salt diet. Unexpectedly, male cortical mitochondria showed significantly higher O2 consumption during ATP synthesis (OXPHOS) than females when fueled by either complex I- or complex II-linked substrates. Cortical H2O2 emission was also greater in males, under both forward and reverse electron transport fueled by succinate. This was accompanied by increased Complex IV protein abundance without changes in mitochondrial DNA copy number or dynamics markers. In the OM, both mitochondrial respiration and H2O2 emission exceeded cortical levels, but showed no sex differences. Analysis of kidney transporter protein abundance revealed a sex-specific "downstream shift" in nephron transport, with males exhibiting greater proximal tubule (PT) sodium reabsorption potential and reduced distal transport capacity. Elevated cortical OXPHOS activity in males likely supports these higher PT energy demands. Thus, sex differences in renal mitochondrial function diverge from other organs, reflecting kidney-specific energetic priorities that override systemic maternal inheritance and sex hormone influences. Enhanced cortical H2O2 emission in males may underlie their heightened susceptibility to kidney injury and salt sensitivity.

Author List

Yang C, Dave DD, Boovarahan SR, Shimada S, Geurts A, Dash RK, Cowley AW Jr

Authors

Sri Rahavi Boovarahan Postdoctoral Researcher 2 in the Biomedical Engineering department at Medical College of Wisconsin
Allen W. Cowley PhD Professor in the Physiology department at Medical College of Wisconsin
Ranjan K. Dash PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin
Devanshi D. Dave Postdoctoral Researcher 4 in the Biomedical Engineering department at Medical College of Wisconsin
Aron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Respiration
Female
Hydrogen Peroxide
Kidney
Male
Mitochondria
Oxidative Phosphorylation
Oxygen Consumption
Rats
Rats, Inbred Dahl
Sex Characteristics
Sex Factors