Methylglyoxal Impairs Mitochondrial Bioenergetics and Microglial Functions
- 1Department of Cellular Neurobiology, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Abstract
Aging is accompanied by a progressive disruption of brain homeostasis, yet the molecular mechanisms underlying this age-associated deterioration remain poorly understood. Microglia play a critical role in maintaining brain homeostasis by clearing cellular debris and neurotoxic protein aggregates. Here, we investigated the effects of methylglyoxal (MG), a highly reactive endogenous metabolite that accumulates with aging, on microglial functions using the murine microglial cell line BV2. We assessed the effects of MG exposure on multiple aspects of microglial biology in both control and bacterial lipopolysaccharide (LPS)-treated cells, including phagocytic activity, cellular proliferation, cytokine secretion, mitochondrial bioenergetics, mitochondrial membrane potential, and intracellular and mitochondrial reactive oxygen species. We found that MG significantly impaired mitochondrial bioenergetics, leading to reduced cellular energy production, and markedly suppressed multiple essential microglial functions, including phagocytosis. Given the high reactivity of MG with arginine, we also investigated whether arginine depletion contributes to these functional impairments. Arginine depletion recapitulated the impairment of mitochondrial bioenergetics and microglial function induced by MG, demonstrating that arginine availability is a critical determinant of microglial metabolic fitness and immune function. These findings suggest that the age-associated accumulation of MG impairs mitochondrial bioenergetics and microglial functions, thereby potentially accelerating neurodegenerative processes.
Related
- The mitochondrial-derived peptide MOTS-c improves bioenergetics in aging-associated granulosa cells and oocytes
- The microglial lineage: from molecular states to context-dependent functions
- Molybdenum and Cadmium Co-exposure Impairs Splenic Mitochondrial Homeostasis and Promotes Ferroptosis-Related Injury in Sheep.
- Increased Expression of Desmin and Vimentin Impairs Mitochondrial Function and Reduces Contractility via G0S2 in Bladder Smooth Muscle.
- Zinc Hexacyanoferrate Nanoenzymes Attenuate Neuroinflammation After Spinal Cord Injury by Modulating Mitochondrial Function and Microglial Polarization.
BibTeX
@article{taguchi2026methylglyoxal,
title = {{Methylglyoxal Impairs Mitochondrial Bioenergetics and Microglial Functions}},
author = {Taketo Taguchi and Pamela Maher},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15211950},
url = {https://www.mdpi.com/2073-4409/15/21/1950},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Methylglyoxal Impairs Mitochondrial Bioenergetics and Microglial Functions
AU - Taketo Taguchi
AU - Pamela Maher
PY - 2026
DA - 2026/10/27
JO - Cells
DO - 10.3390/cells15211950
UR - https://www.mdpi.com/2073-4409/15/21/1950
AB - Aging is accompanied by a progressive disruption of brain homeostasis, yet the molecular mechanisms underlying this age-associated deterioration remain poorly understood. Microglia play a critical role in maintaining brain homeostasis by clearing cellular debris and neurotoxic protein aggregates. Here, we investigated the effects of methylglyoxal (MG), a highly reactive endogenous metabolite that accumulates with aging, on microglial functions using the murine microglial cell line BV2. We assessed the effects of MG exposure on multiple aspects of microglial biology in both control and bacterial lipopolysaccharide (LPS)-treated cells, including phagocytic activity, cellular proliferation, cytokine secretion, mitochondrial bioenergetics, mitochondrial membrane potential, and intracellular and mitochondrial reactive oxygen species. We found that MG significantly impaired mitochondrial bioenergetics, leading to reduced cellular energy production, and markedly suppressed multiple essential microglial functions, including phagocytosis. Given the high reactivity of MG with arginine, we also investigated whether arginine depletion contributes to these functional impairments. Arginine depletion recapitulated the impairment of mitochondrial bioenergetics and microglial function induced by MG, demonstrating that arginine availability is a critical determinant of microglial metabolic fitness and immune function. These findings suggest that the age-associated accumulation of MG impairs mitochondrial bioenergetics and microglial functions, thereby potentially accelerating neurodegenerative processes.
SN - 2073-4409
ER -