How the mitochondrion was shaped by radical differences in substrates

Speijer, Dave

doi:10.1002/bies.201400033

Cited by 37 publications

(29 citation statements)

References 97 publications

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“…First of all, ROS formation is not a peripheral bacterial phenomenon anymore: it now occurs in the middle of the new organism. Secondly, alternatively using different catabolic substrates, as described above, gave rise to more ROS formation [5,6]. Why should this be so?…”

Section: A Kinetic Theory In Which Fadh2/nadh Ratios Determine Mitochmentioning

confidence: 99%

“…Thus, increased electron fluxes using Complex I, II, and ETF directly lead to a general increase in both the QH 2 /Q and NADH/NAD + ratios (see Figure 1B). This in turn would lead to radical formation when oxidation of QH 2 cannot keep up [6]. When the oxidation rate of QH 2 by Complex III (CoQH 2 –cytochrome c reductase) is sufficient to suppress ROS formation upstream during glucose catabolism, the same oxidation rate would not necessarily suffice during FA breakdown [5] (see also [9]).…”

Section: A Kinetic Theory In Which Fadh2/nadh Ratios Determine Mitochmentioning

confidence: 99%

“…FFAs or CoA esters cannot be used because of uncoupling effects and because FAs have to be imported as activated carnitine esters. However, as discussed below, there are quite a few indications that carnitine (see Figure 3A) functions as an effective antioxidant that aggregates in the mt matrix upon import and will efficiently compete with the ROS detection systems used [6,81,82].

Figure 3.Structural formulas of carnitine and simple acylcarnitine esters.( A ) Carnitine, ( B ) l -acetylcarnitine, and ( C ) l -propionylcarnitine as intermediates of fatty acid metabolism and related ROS scavengers.…”

Section: Ros Formation In Isolated Mitochondria Oxidizing Fas: Is Thementioning

confidence: 99%

“…Another inner membrane protein, CPT2, reacting with CoA, gives acyl-CoA and releases carnitine. This is quite an elaborate and complex scheme, but it has real evolutionary advantages which can be deduced from the following [6]. CACT does not only exchange acylcarnitines for carnitines by an antiport function, but it also exhibits low-rate uniport carnitine transport [164].…”

Section: Did Carnitine Evolve As An Efficient Ros Scavenger In the Comentioning

confidence: 99%

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Being right on Q: shaping eukaryotic evolution

Speijer

2016

Biochemical Journal

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Reactive oxygen species (ROS) formation by mitochondria is an incompletely understood eukaryotic process. I proposed a kinetic model [BioEssays (2011) 33, 88–94] in which the ratio between electrons entering the respiratory chain via FADH2 or NADH (the F/N ratio) is a crucial determinant of ROS formation. During glucose breakdown, the ratio is low, while during fatty acid breakdown, the ratio is high (the longer the fatty acid, the higher is the ratio), leading to higher ROS levels. Thus, breakdown of (very-long-chain) fatty acids should occur without generating extra FADH2 in mitochondria. This explains peroxisome evolution. A potential ROS increase could also explain the absence of fatty acid oxidation in long-lived cells (neurons) as well as other eukaryotic adaptations, such as dynamic supercomplex formation. Effective combinations of metabolic pathways from the host and the endosymbiont (mitochondrion) allowed larger varieties of substrates (with different F/N ratios) to be oxidized, but high F/N ratios increase ROS formation. This might have led to carnitine shuttles, uncoupling proteins, and multiple antioxidant mechanisms, especially linked to fatty acid oxidation [BioEssays (2014) 36, 634–643]. Recent data regarding peroxisome evolution and their relationships with mitochondria, ROS formation by Complex I during ischaemia/reperfusion injury, and supercomplex formation adjustment to F/N ratios strongly support the model. I will further discuss the model in the light of experimental findings regarding mitochondrial ROS formation.

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Section: A Kinetic Theory In Which Fadh2/nadh Ratios Determine Mitochmentioning

confidence: 99%

Section: A Kinetic Theory In Which Fadh2/nadh Ratios Determine Mitochmentioning

confidence: 99%

Section: Ros Formation In Isolated Mitochondria Oxidizing Fas: Is Thementioning

confidence: 99%

Section: Did Carnitine Evolve As An Efficient Ros Scavenger In the Comentioning

confidence: 99%

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Being right on Q: shaping eukaryotic evolution

Speijer

2016

Biochemical Journal

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“…BG, bacterial genome; BO, fatty-acid/b-oxidation; DC, diploid chromosomes; FM, mitochondrial fusion/fission cycles followed by mitophagy; Gr, mitochondrial genome reduction; Mi, mitochondrion; Nm, nuclear membrane; RC, respiratory chain; ROS, reactive oxygen species. See main text; adapted from Speijer [53].…”

Section: Indirect Evidence From 'Asexual' Eukaryotesmentioning

confidence: 99%

What can we infer about the origin of sex in early eukaryotes?

Speijer

2016

Phil. Trans. R. Soc. B

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One contribution of 15 to a theme issue 'Weird sex: the underappreciated diversity of sexual reproduction'. Current analysis shows that the last eukaryotic common ancestor (LECA) was capable of full meiotic sex. The original eukaryotic life cycle can probably be described as clonal, interrupted by episodic sex triggered by external or internal stressors. The cycle could have started in a highly flexible form, with the interruption of either diploid or haploid clonal growth determined by stress signals only. Eukaryotic sex most likely evolved in response to a high mutation rate, arising from the uptake of the endosymbiont, as this ( proto) mitochondrion generated internal reactive oxygen species. This is consistent with the likely development of full meiotic sex from a diverse set of existing archaeal (the host of the endosymbiont) repair and signalling mechanisms. Meiotic sex could thus have been one of the fruits of symbiogenesis at the basis of eukaryotic origins: a product of the merger by which eukaryotic cells arose. Symbiogenesis also explains the large-scale migration of organellar DNA to the nucleus. I also discuss aspects of uniparental mitochondrial inheritance and mitonuclear interactions in the light of the previous analysis.This article is part of the themed issue 'Weird sex: the underappreciated diversity of sexual reproduction'.

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The evolution of eukaryotic cells from the perspective of peroxisomes

2014

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Beta-oxidation of fatty acids and detoxification of reactive oxygen species are generally accepted as being fundamental functions of peroxisomes. Additionally, these pathways might have been the driving force favoring the selection of this compartment during eukaryotic evolution. Here we performed phylogenetic analyses of enzymes involved in beta-oxidation of fatty acids in Bacteria, Eukaryota, and Archaea. These imply an alpha-proteobacterial origin for three out of four enzymes. By integrating the enzymes' history into the contrasting models on the origin of eukaryotic cells, we conclude that peroxisomes most likely evolved non-symbiotically and subsequent to the acquisition of mitochondria in an archaeal host cell.

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How the mitochondrion was shaped by radical differences in substrates

Cited by 37 publications

References 97 publications

Being right on Q: shaping eukaryotic evolution

Being right on Q: shaping eukaryotic evolution

What can we infer about the origin of sex in early eukaryotes?

The evolution of eukaryotic cells from the perspective of peroxisomes

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