Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Crit Care Med. Sep 9, 2026; 15(3): 120314
Published online Sep 9, 2026. doi: 10.5492/wjccm.120314
Published online Sep 9, 2026. doi: 10.5492/wjccm.120314
Dissipation of the mitochondrial proton motive force drives sepsis pathogenesis and explains hyperlactatemia’s predictive value in sepsis mortality
Jay Pravda, Department of Disease Pathogenesis, Inflammatory Disease Research Centre, Palm Beach Gardens, FL 33410, United States
Author contributions: Pravda J is the sole author of this manuscript and solely responsible for its content; Pravda J performed all the research, collected, analyzed, and interpreted all the data; Pravda J conceived of and developed the hydrogen peroxide-based pathogenesis of sepsis; Pravda J prepared and wrote the manuscript and performed all critical revisions; Pravda J certifies that this manuscript is the product of his original research; and Pravda J has overall responsibility for this manuscript.
Conflict-of-interest statement: The corresponding author states that there is no conflict of interest.
Corresponding author: Jay Pravda, MD, Senior Scientist, Department of Disease Pathogenesis, Inflammatory Disease Research Centre, 4371 Northlake Blvd No. 247, Palm Beach Gardens, FL 33410, United States. jay.pravda@protonmail.com
Received: February 24, 2026
Revised: March 12, 2026
Accepted: April 21, 2026
Published online: September 9, 2026
Processing time: 179 Days and 10.2 Hours
Revised: March 12, 2026
Accepted: April 21, 2026
Published online: September 9, 2026
Processing time: 179 Days and 10.2 Hours
Core Tip
Core Tip: Despite extensive research spanning several decades and numerous unsuccessful clinical trials, the underlying cause of sepsis remains elusive. However, the characteristic metabolic disturbances observed in sepsis—such as hyperlactatemia, bioenergetic failure, metabolic acidosis, hypothermia, and oxidative stress—can be explained by dissipation of the mitochondrial proton motive force. Emerging evidence suggests that hydrogen peroxide–mediated disruption of this proton gradient represents the proximal mechanism driving the pathogenesis of sepsis.