Researchers have identified a mechanism called excitation-mitochondrial DNA transcription coupling (E-TCmito) that links neuronal activity with mitochondrial DNA transcription, crucial for brain function. Enhancing E-TCmito in aged mice improved cognitive abilities, presenting a potential therapeutic target for combating cognitive decline and neurodegenerative diseases like Alzheimer’s. As mammals age, mitochondrial metabolism in the brain becomes less efficient, impacting neuron and network functions, and leading to oxidative stress and mitochondrial dysfunction. Understanding the decline in oxidative phosphorylation (OXPHOS) activity and its effects on mitochondrial efficiency has historically been limited, hampering targeted interventions for age-related cognitive issues. Wenwen Li and her team explored the role of mitochondrial transcription in the hippocampi of young and aged mice, discovering E-TCmito as a novel coupling mechanism that connects neuronal excitation to mitochondrial DNA transcription. This coupling, which differs from traditional neuron-nucleus excitation-transcription mechanisms, is vital for synaptic and mitochondrial health. The study showed that the efficacy of E-TCmito diminishes with age, contributing to cognitive decline. By enhancing this mechanism, researchers observed significant cognitive improvements in older mice, potentially paving the way for interventions to target age-related neurocognitive disorders tied to mitochondrial dysfunction.
