High-glucose diets induce mitochondrial dysfunction in Caenorhabditis elegans.

Jonathan Alcántar-Fernández,Martha Elva Pérez Andrade,Angélica González-Maciel,Antonio Velázquez-Arellano,Alain De J Hernández-Vázquez,Rafael Reynoso-Robles,Juan Miranda-Ríos,Nobuyuki Takahashi

doi:10.1371/journal.pone.0226652

Jonathan Alcántar-Fernández, Martha Elva Pérez Andrade + Show 6 more

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https://doi.org/10.1371/journal.pone.0226652

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Abstract

Glucose is an important nutrient that dictates the development, fertility and lifespan of all organisms. In humans, a deficit in its homeostatic control might lead to hyperglucemia and the development of obesity and type 2 diabetes, which show a decreased ability to respond to and metabolize glucose. Previously, we have reported that high-glucose diets (HGD) induce alterations in triglyceride content, body size, progeny, and the mRNA accumulation of key regulators of carbohydrate and lipid metabolism, and longevity in Caenorhabditis elegans (PLoS ONE 13(7): e0199888). Herein, we show that increasing amounts of glucose in the diet induce the swelling of both mitochondria in germ and muscle cells. Additionally, HGD alter the enzymatic activities of the different respiratory complexes in an intricate pattern. Finally, we observed a downregulation of ceramide synthases (hyl-1 and hyl-2) and antioxidant genes (gcs-1 and gst-4), while mitophagy genes (pink-1 and dct-1) were upregulated, probably as part of a mitohormetic mechanism in response to glucose toxicity.

Highlights

Mitochondria are essential eukaryotic organelles that participate in the production of energy (by means of the tricarboxylic acid cycle, beta-oxidation, the electron transport chain (ETC)), and in diverse cellular events such as Ca2+ and redox homeostasis, apoptosis, the biosynthesis of heme, amino acids, and phospholipids [1,2]
To determine if glucose affects the morphology of mitochondria, worms were grown in media supplemented with glucose 20, 40, 80 or 100 mM, and the morphology of germ cells and muscle cells was observed through a transmision electron microscope
Subtle changes in mitochondrial morphology were observed at glucose 40 mM, which became more prominent at 80 mM (Fig 1C and 1D)

Summary

Introduction

Mitochondria are essential eukaryotic organelles that participate in the production of energy (by means of the tricarboxylic acid cycle, beta-oxidation, the electron transport chain (ETC)), and in diverse cellular events such as Ca2+ and redox homeostasis, apoptosis, the biosynthesis of heme, amino acids, and phospholipids [1,2]. Mitochondria are composed of a double membrane structure, consisting of the inner and outer mitochondrial membranes (IM and OM, respectively), which differ in function and shape. While the OM is relatively smooth, the IM is highly folded on the inside to form the crista structures that maximize the surface area, which contributes to an efficient oxidative phosphorylation [1].

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