Fluid Restriction Enhances Mitochondrial Stress in Peripheral Blood Mononuclear Cells Following High-volume Resistance Exercise in Health Young Males

Document Type

Article

Publication Date

6-1-2026

Publication Source

American Journal of Physiology Cell Physiology

Volume Number

330

Issue Number

6

First Page

C1631

Last Page

C1646

ISSN

03636143

E-ISSN

15221563

Abstract

Exercising under dehydrated conditions is common among physically active individuals, yet its impact on immune cell mitochondrial quality control, oxidative stress and inflammatory signaling, and systemic inflammatory mediators remains poorly defined. This study investigated mitochondrial quality control and systemic inflammatory responses to high-volume resistance exercise (HVRE) under hydrated (HYD) and dehydrated (DEH) conditions in 10 young men (21 ± 1 yr, 175 ± 6 cm, 76.9 ± 10.5 kg, 18.5 ± 6.3% fat). Participants completed two identical HVRE sessions following either normal hydration or 24-h fluid restriction. Peripheral blood mononuclear cells (PBMCs) collected before (PRE) and at 1 h and 3 h post-HVRE were analyzed for proteins related to mitochondrial quality control (PINK1, Parkin, DRP1, p-DRP1S616, and MFN2), oxidative stress and inflammatory signaling (p-NF-κBS536, NF-κB, SOD2, and H2O2), autophagy machinery and degradation (LC3-I, LC3-II, p62, and cathepsin-L), and blood samples for systemic inflammatory mediators (IL-6, TNF-a, CRP, and H2O2). Significant time × condition interaction effects revealed that LC3-II/I was greater in DEH than HYD at PRE and 3 h. In DEH, LC3-II/I returned to PRE levels at 3 h, whereas in HYD, it was greatest at 3 h. PINK1 was greater at 1 h and 3 h, and pDRP1S616 was greater at 3 h in DEH than HYD. Also, PINK1 and pDRP1S616 were greatest at 3 h post-HVRE in DEH. Lastly, significant condition main effects revealed greater MFN2, p62, LC3-II, and H2O2 in PBMCs and greater IL-6 and CRP in serum in DEH than in HYD. These results provide novel evidence that 24 h of fluid restriction before metabolically demanding resistance exercise activates mitochondrial quality control in PBMCs and elevates systemic inflammatory mediators.

Keywords

hypohydration, IL-6, mitochondria dynamics, mitophagy, ROS

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