Herpe 2024 Abstract IOC163

From Bioblast
Herpe L, Pichaud N (2024) Investigating the importance of mtG3PDH in mitochondrial flexibility during environmental and physiological changes. Mitochondr Physiol Network 28.11.

Link: IOC163

Herpe Lea, Pichaud Nicolas (2024)

Event: IOC163

Maintaining cellular homeostasis is crucial to survival, and organisms must be able to adjust their physiology and metabolism to environmental and cellular constraints. Mitochondria are at the core of these adjustments, as they integrate multiple pathways and perform one of life’s most important biological functions, the production of ATP via the oxidative phosphorylation process (OXPHOS). When confronted to stressful conditions such as reduced macronutrient availability or impairment of cellular signaling, these organelles can lose their ability to modulate substrate oxidation switching from NADH-bound to FADH2-bound substrates, a process known as mitochondrial inflexibility(1). Recently, it was shown that feeding Drosophila melanogaster with high-fat or high-sugar diets for prolonged periods induces mitochondrial inflexibility, characterized by complex I dysfunction which is however offset by an increased contribution of alternative mitochondrial complexes such as mitochondrial glycerol-3-phosphate dehydrogenase (mtG3PDH). As a result, mtG3PDH seems to be involved in metabolic adjustments and would be a protein playing an important role in adaptation to environmental challenges. Moreover, few studies so far have examined the relationship between mitochondrial function and gender. Recently, studies on human mitochondrial biology have unveiled sex-specific differences. According to Ventura-Clapier et al. (2017)(2), rat brain mitochondria display reduced oxidative damage. Furthermore, Junker et al. (2022)(3) observed elevated mitochondrial content in female brown adipose tissue and increased ROS production in male skeletal muscle. Indeed, there is evidence of physiological differences at the mitochondrial level between males and females, mainly in mammals, but the mechanisms that drive these differences and underpin distinct mitochondrial functioning between individuals have yet to be explored.

Mitochondria are therefore central to sex differences, dictating in part the trajectory of organisms’ life-history traits, as well as the response to environmental changes such as temperature and food resources, which greatly influence the physiology and metabolism of organisms, and hence their survival. However, the importance of metabolic flexibility, and more specifically of changes in substrate oxidation by mitochondria according to environmental and cellular conditions, has seldomly been studied. The aim of this project is therefore to characterize the role of mtG3PDH in mitochondrial substrate oxidation and individual performance in response to environmental changes, and its involvement in the cellular aging process as a function of gender. To achieve this, we generated D. melanogaster lines with impaired mtG3PDH activity using the Crispr-Cas9 technique. After obtaining multiple modified lines, we confirmed the reduction of mtG3PDH activity through spectrophotometry and selected potential candidate lines. Subsequently, we plan to expose the mt-G3PDH KD flies to various diets (standard, high-fat, high-sucrose) or different temperatures (15, 24, and 30Β°C). We will conduct experiments at both the individual and isolated mitochondrial levels to evaluate the role of mtG3PDH in mitochondrial substrate oxidation in response to diet and temperature variations and its involvement in organismal performance. Finally, we aim to determine the influence of sex on mitochondrial function and explore mtG3PDH involvement in sex-specific cellular aging processes. For this purpose, we will compare the longevity of male and female mtG3PDH-KD flies with wild-type flies and measure multiple mitochondrial parameters at different ages.


β€’ Bioblast editor: Plangger M


Labels: MiParea: Gender, Respiration, Genetic knockout;overexpression, Comparative MiP;environmental MiP, Exercise physiology;nutrition;life style 




Regulation: Temperature 


HRR: Oxygraph-2k 


Affiliations

Herpe L1,2, Pichaud N1,2
  1. New Brunswick Centre of Precision Medicine, Moncton, NB, Canada.
  2. Department of Chemistry and Biochemistry, UniversitΓ© de Moncton, Moncton, NB, Canada.

References

  1. Simard, C. J., Touaibia, M., Allain, E. P., Hebert-Chatelain, E. & Pichaud, N. Role of the Mitochondrial Pyruvate Carrier in the Occurrence of Metabolic Inflexibility in Drosophila melanogaster Exposed to Dietary Sucrose. Metabolites 10, 411 (2020).
  2. Ventura-Clapier, R. et al. Mitochondria: a central target for sex differences in pathologies. Clinical Science 131, 803–822 (2017).
  3. Junker, A. et al. Human studies of mitochondrial biology demonstrate an overall lack of binary sex differences: A multivariate meta‐analysis. The FASEB Journal 36, (2022).
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