Forward operation of adenine nucleotide translocase during F0F1-ATPase reversal: critical role of matrix substrate-level phosphorylation

被引：83

作者：

Chinopoulos, Christos ^{[1
]}

Gerencser, Akos A. ^{[3
]}

Mandi, Miklos ^{[1
]}

Mathe, Katalin ^{[1
]}

Torocsik, Beata ^{[1
]}

Doczi, Judit ^{[1
]}

Turiak, Lilla ^{[1
]}

Kiss, Gergely ^{[1
]}

Konrad, Csaba ^{[1
]}

Vajda, Szilvia ^{[1
]}

Vereczki, Viktoria ^{[2
]}

Oh, Richard J. ^{[3
]}

Adam-Vizi, Vera ^{[1
]}

机构：

[1] Semmelweis Univ, Hungarian Acad Sci, Szentagothai Knowledge Ctr, Dept Med Biochem,Neurobiochem Grp, H-1094 Budapest, Hungary

[2] Semmelweis Univ, Fac Med, Dept Anat Histol & Embryol, H-1094 Budapest, Hungary

[3] Buck Inst Age Res, Novato, CA USA

来源：

FASEB JOURNAL | 2010年 / 24卷 / 07期

基金：

美国国家卫生研究院; 匈牙利科学研究基金会;

关键词：

adenine nucleotide carrier; ATP synthasome; systems biology of mitochondria; SUCLA2; bioenergetics; HEART-RATE HEARTS; MITOCHONDRIAL ADENOSINE 5'-TRIPHOSPHATASE; CA-2&-INDUCED MEMBRANE TRANSITION; ALPHA-KETOGLUTARATE DEHYDROGENASE; CULTURED CORTICAL-NEURONS; SUCCINYL-COA SYNTHETASES; K-ATP CHANNELS; INTRACELLULAR ATP; IN-VITRO; CALCIUM DEREGULATION;

D O I：

10.1096/fj.09-149898

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In pathological conditions, F0F1-ATPase hydrolyzes ATP in an attempt to maintain mitochondrial membrane potential. Using thermodynamic assumptions and computer modeling, we established that mitochondrial membrane potential can be more negative than the reversal potential of the adenine nucleotide translocase (ANT) but more positive than that of the F0F1-ATPase. Experiments on isolated mitochondria demonstrated that, when the electron transport chain is compromised, the F0F1-ATPase reverses, and the membrane potential is maintained as long as matrix substrate-level phosphorylation is functional, without a concomitant reversal of the ANT. Consistently, no cytosolic ATP consumption was observed using plasmalemmal K-ATP channels as cytosolic ATP biosensors in cultured neurons, in which their in situ mitochondria were compromised by respiratory chain inhibitors. This finding was further corroborated by quantitative measurements of mitochondrial membrane potential, oxygen consumption, and extracellular acidification rates, indicating nonreversal of ANT of compromised in situ neuronal and astrocytic mitochondria; and by bioluminescence ATP measurements in COS-7 cells transfected with cytosolic- or nuclear-targeted luciferases and treated with mitochondrial respiratory chain inhibitors in the presence of glycolytic plus mitochondrial vs. only mitochondrial substrates. Our findings imply the possibility of a rescue mechanism that is protecting against cytosolic/nuclear ATP depletion under pathological conditions involving impaired respiration. This mechanism comes into play when mitochondria respire on substrates that support matrix substrate-level phosphorylation.-Chinopoulos, C., Gerencser, A.A., Mandi, M., Mathe, K., Torocsik, B., Doczi, J., Turiak, L., Kiss, G., Konrad, C., Vajda, S., Vereczki, V., Oh, R. J., Adam-Vizi, V. Forward operation of adenine nucleotide translocase during F0F1-ATPase reversal: critical role of matrix substrate-level phosphorylation. FASEB J. 24, 2405-2416 (2010). www.fasebj.org

引用

页码：2405 / 2416

页数：12

共 65 条

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