How to deal with oxygen radicals stemming from mitochondrial fatty acid oxidation

Abstract

Oxygen radical formation in mitochondria is an incompletely understood attribute of eukaryotic cells. Recently, a kinetic model was proposed, in which the ratio between electrons entering the respiratory chain via FADH 2 or NADH determines radical formation. During glucose breakdown, the ratio is low; during fatty acid breakdown, the ratio is high (the ratio increasing—asymptotically—with fatty acid length to 0.5, when compared with 0.2 for glucose). Thus, fatty acid oxidation would generate higher levels of radical formation. As a result, breakdown of fatty acids, performed without generation of extra FADH 2 in mitochondria, could be beneficial for the cell, especially in the case of long and very long chained ones. This possibly has been a major factor in the evolution of peroxisomes. Increased radical formation, as proposed by the model, can also shed light on the lack of neuronal fatty acid oxidation and tells us about hurdles during early eukaryotic evolution. We specifically focus on extending and discussing the model in light of recent publications and findings.

Sex is a ubiquitous, ancient, and inherent attribute of eukaryotic life

“…Examples of such pressures are the possible influx of introns coming from the α-proteobacterial endosymbiont, leading to formation of the nucleus (100) or enhanced intracellular ROS formation leading among others to the evolution of peroxisomes (101,102), intracellular compartmentalization, mitochondrial genome reduction and uncoupling, DNA protection by nuclear membrane formation, and extensive increases in antioxidant mechanisms (103). Mounting evidence strongly indicates that peroxisomes are indeed a eukaryotic invention in response to entry of the premitochondrion (104)(105)(106). The symbiogenic model is also not plagued by a possible conceptual bioenergetics problem: how to pay for all of the expensive eukaryotic inventions without the presumably more efficient energy generation resulting from integrating different metabolic pathways and obtaining internal mitochondrial membranes (107).…”

The oxidative debt of fasting: evidence for short to medium-term costs of advanced fasting in adult king penguins

“…Indeed, oxidative stress, i.e. an imbalance between ROS and counteracting defences, in PIII individuals may be associated (1) in the short-term with the transition from PII to PIII and associated increase in metabolic rate (Cherel et al, 1994b;Le Maho et al, 1981); and (2) in the medium-term with the intense foraging effort likely required by PIII birds to recoup their initial body condition (Andreyev et al, 2005;Hulbert et al, 2007;Isaksson et al, 2011;Speijer et al, 2014). Indeed, in addition to high metabolic rates that may result in the by-production of large quantities of ROS (Beckman and Ames, 1998;Stier et al, 2014a,b; but see Speakman and Selman, 2011), king penguins forage in apnoea during repetitive diving bouts (>1000 foraging dives per trip; Bost et al, 2007) carried out at high ambient pressure (>100 m diving depth; Kooyman et al, 1992).…”

Being right on Q: shaping eukaryotic evolution

“…Of note, NNT seems to be highly expressed in neurons of Caenorhabditis elegans and humans [65]. NNT deficiencies can lead to neurological problems, as also illustrated by the extra sensitivity to neurotoxic agents observed in mice in its absence ([62]; see below and [66]). In S. cerevisiae , not only Complex I and NNT have gone, but β-oxidation has been completely (!)…”