Bai 2016 PLOS ONE

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Bai F, Fink BD, Yu L, Sivitz WI (2016) Voltage-dependent regulation of Complex II energized mitochondrial oxygen flux. PLOS ONE 11:e0154982.

» PMID: 27153112 Open Access

Bai F, Fink BD, Yu L, Sivitz WI (2016) PLoS One

Abstract: 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.

Keywords: Amplex Red

O2k-Network Lab: US IA Iowa City Sivitz WI


Labels: MiParea: Respiration, Instruments;methods 

Stress:Oxidative stress;RONS  Organism: Mouse  Tissue;cell: Heart, Skeletal muscle, Nervous system, Liver  Preparation: Isolated mitochondria 

Regulation: ADP  Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, CIV, NS  HRR: Oxygraph-2k, TPP 

2016-07