Oxidative Phosphorylation

Lehninger, Albert L.; Wadkins, Charles L.

doi:10.1146/annurev.bi.31.070162.000403

Cited by 101 publications

(59 citation statements)

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“…Nevertheless, the hypotheses of phase separation and exclusion of aqueous phase continuity for H þ transfer allow to conceive an aerobic ATP synthesis occurring independently of closed compartments where to accumulate H þ is not necessary for ATP synthesis, as also proposed for IMM by Lehninger half a century ago. 56 A vectorial transfer of H þ intrinsic to the IMM following the Grotthus mechanism, with a fine integration of H þ translocation and electron transfer for direct coupling of ETC and ATP synthase, thanks to the lipid environment, underlines the unique role of biological membranes in the evolution of life. These would not only have provided a permeability barrier and compartmentation, but had a fundamental role in arranging the proteins involved in gaining chemical energy for life.…”

Section: Discussionmentioning

confidence: 99%

Hypothesis of Lipid-Phase-Continuity Proton Transfer for Aerobic ATP Synthesis

Morelli

Ravera

Calzia

et al. 2013

J Cereb Blood Flow Metab

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The basic processes harvesting chemical energy for life are driven by proton (H þ ) movements. These are accomplished by the mitochondrial redox complex V, integral membrane supramolecular aggregates, whose structure has recently been described by advanced studies. These did not identify classical aqueous pores. It was proposed that H þ transfer for oxidative phosphorylation (OXPHOS) does not occur between aqueous sources and sinks, where an energy barrier would be insurmountable. This suggests a novel hypothesis for the proton transfer. A lipid-phase-continuity H þ transfer is proposed in which H þ are always bound to phospholipid heads and cardiolipin, according to Mitchell's hypothesis of asymmetric vectorial H þ diffusion. A phase separation is proposed among the proton flow, following an intramembrane pathway, and the ATP synthesis, occurring in the aqueous phase. This view reminiscent of Grotthus mechanism would better account for the distance among the F o and F 1 moieties of F o F 1 -ATP synthase, for its mechanical coupling, as well as the necessity of a lipid membrane. A unique active role for lipids in the evolution of life can be envisaged. Interestingly, this view would also be consistent with the evidence of an OXPHOS outside mitochondria also found in non-vesicular membranes, housing the redox complexes. Journal of Cerebral Blood INTRODUCTIONChemical energy for living matter is mostly supplied by the F o F 1 -ATP synthases (ATP synthases), multimeric proteins, which employ a rotary mechanism driven by proton-motive force. In turn, protons (H þ ) are translocated by electron transport chain (ETC). The structure and organization of ATP synthases, the 'splendid nanomolecular machine' 1 that mechanically synthesize ATP from ADP and Pi are well described, but how its rotation is driven by proton flow and how this energy is converted into catalysis are less clear.2 F 1 moiety is peculiar in that it is the only enzyme as yet known channeling energy to the reactant species by means of mechanical force. The topic of H þ cycling, pivotal in oxidative phosphorylation, is central in energy conversion.

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Section: Discussionmentioning

confidence: 99%

Hypothesis of Lipid-Phase-Continuity Proton Transfer for Aerobic ATP Synthesis

Morelli

Ravera

Calzia

et al. 2013

J Cereb Blood Flow Metab

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“…This is shown in figure 5, which is a schematic representation of the situation which appears to exist in corn mitochondria. The conventions used are those of Chance and Williams (2) except that the initial high energy bond is considered to be with the oxidized form of the carrier (13,19). Cyanide, which should produce reduced conditions, inhibits substrate powered contraction in corn mitochondria (23, Nothing in the work our laboratory has done to date on the swelling-contraction phenomenon indicates that contraction consumes bond energy; that is, I-being utilized in producing contraction.…”

Section: Discussionmentioning

confidence: 99%

Contracted State as an Energy Source for Ca Binding and Ca + Inorganic Phosphate Accumulation by Corn Mitochondria

Kenefick

Hanson

1966

Plant Physiol.

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Swnmary. An investigation has been made of the possibility of tutilizing the potential energy of the contracted state of corn mitochondria to drive Ca + inorganic phosphate accumulation. Contraction was obtained with succinate or NADH oxidation. In the succinate experiments the mitochondria were contracted in buffered KCl layered over sucrose in centrifuge tubes and centrifuged down through distinct wash, reactive and isotope exchange layers. In the NADH experiments, ion accumulation was initiated upon exhaustion of the substrate. The results show that mitochondria in the contracted state will actively bind some 45Ca, but no real accumtulation occurs until inorganic phosphate is available. Substrate powered contraction in the presence of inorganic phosphate also provides a potential for accumulation upon subsequent reaction of the mitochondria with Ca. It is deducted that contraction is due to X-I formation, to which Ca will bind. Subsequent reaction with inorganic phosphate produces CaX-P, which is the transport moiety. When X-P is formed first, Ca also reacts to produce CaX-P. Hence it is immaterial which ion reacts first with the contracted state. Contraction is believed to result from the action of a mechanoenzyme, presumably I-. The stability of CaX-I must be low for the mitochondria swell very rapidly tupon exhatustion of NADH or blocking of stuccinate oxidation by cyanide.Previotus papers from this laboratory have reported the characteristics of corn mitochondria in Ca + Pi accumulation and in swelling-contraction. Substrate-powered calcium accumulation is dependent upon phosphate, and phosphate acctumulation is dependent tupon calcium, or the related strontium ion which is about half as effective (10,25). The mitochondria show no pronounced tuncotupling responses to Ca; the small decline in P /O ratio with 1 myN Ca is due to diversion of phosphate from ATP formation into Pi acctumtulation (7).Swelling is spontaneous in buffered KCl, with rapid contraction not only with ATP and Mg btut also with the simple addition of an oxidizable substrate (23). The ATP-powered contraction is oligomycin sensitive and releases Pi, accounting for the bulk of the ATPase activity (23). The substrate powered contraction is very closely linked to respiration and is inhibited about 40 % by 1 mm phosphate (23,25). Calciuim releases the phosphate inhibition

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“…It is now well established that mitochondria are the site of cellular respiration as well as of the process called oxidative phosphorylation by which energy liberated in respiration is conserved in the form of ATP 1 (2). Normally the respiration of isolated mitochondria is obligatorily coupled to the formation of ATP from ADP and inorganic phosphate, and thus cannot proceed at any appreciable rate if either of the latter components is absent from the incubating medium (3).…”

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confidence: 99%