MLKL overexpression leads to Ca²⁺ and metabolic dyshomeostasis in a neuronal cell model.

ABSTRACT: The necroptotic effector molecule MLKL accumulates in neurons over the lifespan of mice, and its downregulation has the potential to improve cognition through neuroinflammation, and changes in the abundance of synaptic proteins and enzymes in the central nervous system. Notwithstanding, direct evidence of cell-autonomous effects of MLKL expression on neuronal physiology and metabolism are lacking. Here, we tested whether the overexpression of MLKL in the absence of cell death in the neuronal cell line Neuro-2a recapitulates some of the hallmarks of aging at the cellular level. Using genetically-encoded fluorescent biosensors, we monitored the cytosolic and mitochondrial Ca²⁺ levels, along with the cytosolic concentrations of several metabolites involved in energy metabolism (lac

SUBMITTER: Deepa SS 

PROVIDER: S-EPMC10990772 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature