MODERN MITOCHONDRIA

31 May 2019 - By: Alex Evans

MODERN MITOCHONDRIA

By Alex Evans

One of the ‘Science Across Boundaries’ sessions at the 2018 SEB Annual Meeting explored the integral role of mitochondria in environmental adaptation and disease. Whilst some avenues of research have focused on how mitochondrial adaptations and plasticity contribute to tolerance to external stressors, others have investigated how mitochondrial dysfunctions can contribute to a broad range of human diseases. Here are just a few examples from this wonderful interdisciplinary session.

DOUBLE TROUBLE FOR mtDNA

The mitochondria of eukaryotic organisms are crucially important, and interesting, organelles. Mitochondria are especially unique organelles due to their possession of independent genomes, but given that they play such a prominent role in maintaining and regulating processes vital for sustaining life, it’s no surprise that mutations within the mitochondria can have significant effects for the organism as a whole. In fact, mitochondrial DNA (mtDNA) mutations are responsible for a number of severe mitochondrial disorders in humans, making mtDNA research important for the development of future treatments. However, we still have an incomplete picture of how these mtDNA mutations accumulate and affect functions at the level of both organelle and organism.

To address this important gap in the knowledge, researcher France DuFresne (Université du Québec à Rimouski, Canada) decided to investigate and quantify the accumulation of mutations under environmental stress, and to measure the resulting effects on mitochondrial respiration and organismal fitness. Because mitochondria can be found in all known eukaryotic life (save for one fascinating species of Monocercomonoides), a number of model species have been adopted to examine their form and function in the laboratory. One such species is Daphnia pulex, a small crustacean that serves as an important model system in ecotoxicology due to its sensitivity to environmental pollutants and rapid reproductive turnover. “I used to examine mtDNA mutations in order to tell different Daphnia species apart,” explains France, who was keen to utilise their mtDNA for deeper investigations. “Earlier studies had quantified the rate at which mutations are deposited on mtDNA but no one had actually measured the impact of these mutations on the mitochondrial phenotype.”
organisms
France DuFresne’s study organisms, Daphnia Photo: France DuFresne


Although France had a clear investigation in mind, examining the effects of copper exposure, actually carrying it out was another matter. “Since mutations are rare events, it is not easy to measure them,” says France. She teamed up with Melania Cristescu (McGill University, Canada), who had previously carried out her own mutation accumulation experiment. By propagating many lines from single individuals, they were able to bottleneck the population and increase the probability of mutation fixation. Even so, these experiments still had to run for 3 years to ensure enough mutations had been deposited on the mtDNA in both the copper-exposed and control populations. Not content with just one environmental stress, France and her team also examined what the impact of a second environmental factor, temperature, would be on the accumulation of mtDNA mutations. “After 120 generations, we exposed the Daphnia to optimal and high temperatures and then measured parameters related to fitness, such as rate of respiration, time to maturity, reproductive success, and lifespan.”

The culmination of France’s efforts revealed that the Daphnia lines that had accumulated mutations over 3 years had suffered a mitochondrial respiration rate reduction of 10% compared to controls. These findings are important because they effectively demonstrate how mutations can negatively affect mitochondrial metabolic capacity. “Our results show that the mitochondria could not compensate for the mutations accumulated over time and mitochondrial respiration decreased in all lineages as a result,” explains France, adding that this novel research highlights how stressors such as high temperature and environmental contamination can compound the accumulation of these mutations and have harmful consequences for organismal fitness. “We demonstrate that there is a clear need for a better understanding of how mutations affect these crucially important organelles.”

WINGS OR FLINGS

In a world with finite energy, the way that organisms allocate and utilise metabolic energy is critical to their survival. Given that mitochondria are a core organelle for metabolic functions, it is understandable that energetic investments such as reproduction, growth, or dispersal are linked to variations in mitochondrial function. “For example, broiler chickens selected for rapid muscle growth exhibit mitochondria with higher rates of oxidative phosphorylation and lower rates of proton leak than egg-laying chickens,” explains Caroline Williams, a researcher of metabolic physiology (University of California Berkeley, USA). “This suggests that their mitochondria produce energy from food with a higher efficiency and raises the question of why selection on life history produces such shifts in mitochondrial function.”

However, it is certainly not just chickens that exhibit some level of metabolic variation. Field crickets of the genus Gryllus can present as two distinct morphs within a population, with each morph being physiologically tailored to very different goals.

One morph is specialised for reproduction and possesses non-functional wings, whilst the other morph is fully capable of flight and delays reproduction in order to disperse. Caroline explains that their collaborator, Tony Zera, has shown that the dispersal morph upregulates triglyceride synthesis to store fat for flight fuel, whereas the reproductive morph uses nutrients to build proteins and phospholipids to make eggs.1 “These metabolic differences between morphs makes them the perfect system to test the hypothesis that life history demands determine mitochondrial function.”

In order to investigate these morphs, Caroline’s PhD student Lisa Treidel designed a series of laboratory experiments using high-resolution respirometry that monitored how mitochondrial oxidative phosphorylation changed as the crickets grew to maturity. They found that on the first day of adulthood, mitochondrial function was quite similar between the two morphs, but that the dispersal morph would gradually develop a higher rate of oxidative phosphorylation that resulted in an increased capacity for rapid energy production. “Finally, we found that when the dispersal morph switches to reproductive investment at the end of the first week of adulthood, mitochondrial function abruptly shifts and becomes very similar to the reproductive morph once again,” says Caroline. These results suggest that mitochondrial function is intricately related to the demands of the life history strategy. “When the crickets need to produce large amounts of ATP to fuel flight, they have a high capacity for oxidative phosphorylation,” explains Caroline. “When their life history demands switch toward reproduction, mitochondrial function shifts correspondingly.” Interestingly, this would suggest that mitochondria can specialise to suit particular life-history characteristics instead of serving in a ‘Jack-of-all-trades’ capacity.

The results of Caroline and Lisa’s work has opened up many more intriguing questions about the plastic nature of mitochondria in polymorphic organisms, which they hope to explore: “Why is there no ‘Jack-of-all-trades’ type of mitochondria, and where does the constraint lie? Do the mitochondria of the dispersal morph operate at a higher membrane potential?” Additionally, because mitochondrial dysfunction is implicated in diseases such as diabetes, this line of enquiry may help us to understand the role played by natural variation in mitochondrial function in these diseases and potentially provide new therapeutic interventions to alter mitochondrial performance.


1. Zera AJ, Zhao Z. 2003. Morph-dependent fatty acid oxidation in a wing-polymorphic cricket: implications for the trade-off between dispersal and reproduction. J Insect Physiol, 49(10), 933–943.

Category: Cell Biology
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Alex evans

Alex Evans

Alex Evans is a Research Postgraduate at the University of Leeds investigating the energetics of bird flight. In his spare time, Alex enjoys writing about the natural world, contributing to the Bird Brained Science blog and exploring other avenues of science communication.

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SEB Prague 2020

Prague, Czech Republic
7 - 10 July 2020