Cells, tissues, organs · 2025
Mitochondrial Glycosylation in Neuroinflammation Models.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Madabhushi Meghana, Murphy Rachel Erin, Ali Md Akkas, Paneerselvam Muthuvel, Patil Mallikarjun Hanamantagouda, Tyrrell Daniel J, Samal Juhi
Аннотация
INTRODUCTION: Mitochondria are cellular energy factories, but their function declines with age in many tissues as well as disease pathophysiology. Mitochondrial proteins have sugar modifications called glycans, which regulate their function and localization. There is a knowledge gap on the impact of mitochondrial protein glycosylation on mitochondrial function and mediating neuroinflammation. We hypothesize that stimuli-specific neuroinflammatory treatments in microglia induce pathological changes in mitochondrial protein glycosylation and compromise mitochondrial function.
METHODS: The aim of this study was to establish a detailed microglial mitochondrial glycoprofile in different models of inflammation using lectins to identify the glycan-based markers of mitochondrial dysfunction. We use three different pathways of microglial activation: lipopolysaccharide, cytokines, and oxygen-glucose deprivation (OGD), revealing differences in mitochondrial glycosylation in different models of inflamed microglia. Mitochondrial lectin blots and lectin flow analysis were used to quantify the glycosylation changes due to different neuroinflammatory conditions. Seahorse Mito Stress assay was performed to assess mitochondrial function in each of these conditions.
RESULTS: Lectin immunoblots of mitochondrial proteins and lectin flow studies with intact mitochondria were performed in three different neuroinflammation models using BV-2 microglial cells, revealing considerable stimuli-specific, differential mitochondrial glycosylation between these models and healthy controls. It was found that several glycans associated with mitochondria were differentially regulated during microglial activation. The observed changes in glycosylation trends were more drastic in OGD treatment as compared to other treatments, especially for complex and sialylated glycans.
CONCLUSION: This study represents the first functional investigation of mitochondrial glycosylation in microglial inflammation models towards identifying glycosylation-based therapeutic targets.
METHODS: The aim of this study was to establish a detailed microglial mitochondrial glycoprofile in different models of inflammation using lectins to identify the glycan-based markers of mitochondrial dysfunction. We use three different pathways of microglial activation: lipopolysaccharide, cytokines, and oxygen-glucose deprivation (OGD), revealing differences in mitochondrial glycosylation in different models of inflamed microglia. Mitochondrial lectin blots and lectin flow analysis were used to quantify the glycosylation changes due to different neuroinflammatory conditions. Seahorse Mito Stress assay was performed to assess mitochondrial function in each of these conditions.
RESULTS: Lectin immunoblots of mitochondrial proteins and lectin flow studies with intact mitochondria were performed in three different neuroinflammation models using BV-2 microglial cells, revealing considerable stimuli-specific, differential mitochondrial glycosylation between these models and healthy controls. It was found that several glycans associated with mitochondria were differentially regulated during microglial activation. The observed changes in glycosylation trends were more drastic in OGD treatment as compared to other treatments, especially for complex and sialylated glycans.
CONCLUSION: This study represents the first functional investigation of mitochondrial glycosylation in microglial inflammation models towards identifying glycosylation-based therapeutic targets.