Mitochondria are hot!

There have been some very interesting developments in the field of mitochondrial biology in the past two months. This is very exciting for me as someone who works on bioenergetics in a variety of organisms.

The first paper made quite a splash in the community when it came out because the findings suggest that mitochondria operate at much higher temperatures than were previously believed. The paper by Chrétien et al. 2018 appears in PLOS and is entitled “Mitochondria are physiologically maintained at close to 50°C”. I will admit to being pretty open to this idea and it’s because of two reasons. The first is that I perform research on plants and have specifically worked on the enzyme alternative oxidase (AOX). Several plants are capable of shunting electrons through this enzyme and are able to heat inflorescences up to 42°C when ambient temperatures are much lower. Secondly, I’ve always been bothered by the fact that mitochondrial respiration assays using oxygen electrodes are often performed at 37°C regardless of what organism the mitochondria have been isolated from. It doesn’t made sense to me and I question the physiological relevance of assaying mitochondria using a temperature of 37°C when for example the study organism is a fish that has been acclimated to an external temperature of 5-12°C. Mitochondrial respiration is definitely more sluggish when you run these measurements at 5-12°C, but the mitochondria are still active. So for me, someone attempting to tackle the question of what temperature mitochondria actually run at is an important and highly relevant one.

The paper is an elegant one and what struck me in particular is that the authors have attempted to proactively counter the most obvious challenges that they would face from other researchers in the field. It hinges on the supposition that no energy transduction process in nature is 100% efficient and that some of the free energy of the electron transport system (ETS) must therefore be released as heat. They are obviously limited by the technologies currently available, but they have done an excellent job in using both positive and negative controls to validate their experiments and data. They have used the temperature-sensitive probe MitoThermoYellow to attempt to determine the temperature of mitochondria in a mammalian cell line background. As I read the paper, every few minutes I thought of another potential factor that could be responsible for their results, and in the very next sentence they addressed each of my particular concerns; it was a pretty surreal experience. The mitochondrial temperature is directly influenced by the level of operation of the ETS and what components are present (they do some very neat work with the alternative oxidase and uncoupling protein). They do some preliminary enzymology work on crude extracts to demonstrate that several ETS complexes exhibit temperature optima ~50°C, but that this is only true if the mitochondrial membranes are intact. A fascinating next step would be to examine the role of supercomplexes in these effects.

The authors themselves admit that one of the key questions that needs to be considered is whether mitochondria and cells can maintain temperature gradients, or whether any heat would immediately be lost to the rest of the organisms and/or the environment? Here we need to consider what is known about the physical shape, size, number, and localization of mitochondria in cells and what is known about the insulating capabilities of phospholipids, membrane components, and the contents and composition of various cellular compartments. Much of this information is lacking. These issues and other possible critiques of the paper are addressed by Nick Lane in his article “Hot mitochondria?”. Lots of new questions and concepts brought up by the Chrétien et al. paper which makes it a very valuable contribution to the field.

The second article is one by Cory Dunn entitled “Some Liked It Hot: A Hypothesis Regarding Establishment of the Proto-Mitochondrial Endosymbiont During Eukaryogenesis”. This paper was a lot of fun to read and presents a simple, but profound hypothesis: the initial usefulness of the proto-mitochondrion and the evolutionary driving force for its retention was due to its ability to generate heat and that it wasn’t until much later in evolutionary history that its ability to biosynthesize ATP could be harnessed. It’s a pretty neat idea and the figures in the article help the reader considerably. The premise of this article will be further supported if the conclusion of the Chrétien et al. holds up over time.

 

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