Document Type


Peer Reviewed


Publication Date


NLM Title Abbreviation

PLoS One

Journal/Book/Conference Title

PLoS One

PubMed ID


DOI of Published Version


Start Page


Total Pages



Oxygen consumption by isolated mitochondria is generally measured during state 4 respiration (no ATP production) or state 3 (maximal ATP production at high ADP availability). However, mitochondria in vivo do not function at either extreme. Here we used ADP recycling methodology to assess muscle mitochondrial function over intermediate clamped ADP concentrations. In so doing, we uncovered a previously unrecognized biphasic respiratory pattern wherein O2 flux on the complex II substrate, succinate, initially increased and peaked over low clamped ADP concentrations then decreased markedly at higher clamped concentrations. Mechanistic studies revealed no evidence that the observed changes in O2 flux were due to altered opening or function of the mitochondrial permeability transition pore or to changes in reactive oxygen. Based on metabolite and functional metabolic data, we propose a multifactorial mechanism that consists of coordinate changes that follow from reduced membrane potential (as the ADP concentration in increased). These changes include altered directional electron flow, altered NADH/NAD+ redox cycling, metabolite exit, and OAA inhibition of succinate dehydrogenase. In summary, we report a previously unrecognized pattern for complex II energized O2 flux. Moreover, our findings suggest that the ADP recycling approach might be more widely adapted for mitochondrial studies.



Granting or Sponsoring Agency

United States (U.S.) Department of Veterans Affairs Biomedical Laboratory Research and Development Service

Grant Number

Merit Review Award #5I01BX000285-06


This work was supported by Merit Review Award #5I01BX000285-06 from the United States (U.S.) Department of Veterans Affairs Biomedical Laboratory Research and Development Service, by the Iowa Affiliate Fraternal Order of the Eagles, and by Roy and Lucille Carver College of Medicine Pilot Funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Journal Article Version

Version of Record

Published Article/Book Citation

Bai F, Fink BD, Yu L, Sivitz WI (2016) Voltage-Dependent Regulation of Complex II Energized Mitochondrial Oxygen Flux. PLoS ONE 11(5): e0154982. doi:10.1371/journal.pone.0154982


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Creative Commons License
This work is licensed under a Creative Commons 1.0 Public Domain Dedication.