A perspective on Peter Mitchell and the chemiosmotic theory

Rich, Peter R.

doi:10.1007/s10863-008-9173-7

Cited by 20 publications

(14 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has been said that:'.. (Mitchell's) experimental and conceptual work proved extraordinarily successful in providing proof of the general hypothesis and prompting mechanisms of key components..'. 4 It is worth pointing out that the model proposed here does not conflict with Mitchell's theory. Rather, it reveals the still unrecognized potential of Mitchell's theory, also in being extendable to the emerging awareness of extramitochondrial OXPHOS.…”

Section: Discussionmentioning

confidence: 49%

“…The topic of H þ cycling, pivotal in oxidative phosphorylation, is central in energy conversion. 3,4 Mitchell's chemiosmotic theory foresaw the existence of an H þ translocation by the ETC, coupled to the transfer of electrons to oxygen with the formation of water, being the energy involved in the process in the form of H þ flux, converted to ATP by F o F 1 -ATP synthase nanomotor. 3 H þ was also pivotal for the origin of life.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Morelli

Ravera

Calzia

et al. 2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 49%

Section: Introductionmentioning

confidence: 99%

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

Morelli

Ravera

Calzia

et al. 2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…First, the mitochondrial dysfunction theory of insulin resistance implies that mitochondrial content and/or capacity dictates resting rates of fat oxidation. However, this prediction goes against the widely accepted chemiosmotic model of respiration [75], which holds that absolute rates of fuel oxidation under aerobic conditions depend ultimately on ATP turnover (i.e., workload). A high work rate increases the intramitochondrial ADP/ATP ratio, which promotes proton influx from the inner mitochondrial space through ATP synthase.…”

Section: Mitochondrial Dysfunction: Cause or Consequence Of Metabomentioning

confidence: 92%

Intramuscular triacylglycerol and insulin resistance: Guilty as charged or wrongly accused?

Muoio¹

2010

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

123

101

View full text Add to dashboard Cite

The term lipotoxicity elicits visions of steatotic liver, fat laden skeletal muscles and engorged lipid droplets that spawn a number of potentially harmful intermediates that can wreak havoc on signal transduction and organ function. Prominent among these so-called lipotoxic mediators are signaling molecules such as long chain acyl-CoAs, ceramides and diacyglycerols; each of which is thought to engage serine kinases that disrupt the insulin signaling cascade, thereby causing insulin resistance. Defects in skeletal muscle fat oxidation have been implicated as a driving factor contributing to systemic lipid imbalance, whereas exercise-induced enhancement of oxidative potential is considered protective. The past decade of diabetes research has focused heavily on the foregoing scenario, and indeed the model is grounded in strong experimental evidence, albeit largely correlative. This review centers on mechanisms that connect lipid surplus to insulin resistance in skeletal muscle, as well as those that underlie the antilipotoxic actions of exercise. Emphasis is placed on recent studies that challenge accepted paradigms.

show abstract

“…The octanol/water partition coefficients of methyl and ethylmercury are 1.4 to 1.8 [21, 23], at intracellular pH and [Cl − ], thus both organomercury compounds will predominately exist as lipophilic cations inside cells. Mitchell demonstrated that lipophilic cations accumulate inside mitochondria, in a Nernstian fashion, driven by the steady state membrane potential [24]. Given that the typical mitochondrial membrane potential of astrocytes and neurons is between 140–170 mV [25], one would, a prior , expect the concentration of these organomercury compounds within mitochondria to be approximately 1000 times greater than the cytosolic concentration.…”

Section: Introductionmentioning

confidence: 99%

“…The damage of a cell's mitochondria leads to the activation of the apoptotic cascade and subsequent cell death [3, 4, 24, 26–31]. This may be clinically relevant in the setting of a patient who harbors a known or unknown mitochondrial disorder.…”

Section: Introductionmentioning

confidence: 99%

Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA

Sharpe

Livingston

Baskin

2012

Journal of Toxicology

View full text Add to dashboard Cite

Thimerosal generates ethylmercury in aqueous solution and is widely used as preservative. We have investigated the toxicology of Thimerosal in normal human astrocytes, paying particular attention to mitochondrial function and the generation of specific oxidants. We find that ethylmercury not only inhibits mitochondrial respiration leading to a drop in the steady state membrane potential, but also concurrent with these phenomena increases the formation of superoxide, hydrogen peroxide, and Fenton/Haber-Weiss generated hydroxyl radical. These oxidants increase the levels of cellular aldehyde/ketones. Additionally, we find a five-fold increase in the levels of oxidant damaged mitochondrial DNA bases and increases in the levels of mtDNA nicks and blunt-ended breaks. Highly damaged mitochondria are characterized by having very low membrane potentials, increased superoxide/hydrogen peroxide production, and extensively damaged mtDNA and proteins. These mitochondria appear to have undergone a permeability transition, an observation supported by the five-fold increase in Caspase-3 activity observed after Thimerosal treatment.

show abstract

A perspective on Peter Mitchell and the chemiosmotic theory

Cited by 20 publications

References 16 publications

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

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

Intramuscular triacylglycerol and insulin resistance: Guilty as charged or wrongly accused?

Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA

Contact Info

Product

Resources

About