Axonal Distribution Of Mitochondria Maintains Neuronal Autophagy During Aging Via Eif2Β
As we age, our brain cells, or neurons, face increasing challenges in maintaining their health and function. A key process for cellular upkeep is called autophagy, which is like the cell’s recycling system, clearing out damaged components and aggregated proteins. When this system falters, it can lead to the accumulation of harmful substances and contribute to age-related brain decline.
Recent research sheds light on a critical mechanism that helps keep this recycling system running smoothly in the long, slender projections of neurons called axons, which are responsible for transmitting signals. It turns out that the proper placement and function of mitochondria—the “powerhouses” of the cell—within these axons are vital. When these mitochondria are depleted from the axons, the cellular recycling process, autophagy, is significantly reduced, leading to a buildup of aggregated proteins.
The study identified a specific protein, eIF2β, as a key player in this process. When axonal mitochondria are lost, the levels of eIF2β increase, and this increase is directly linked to the decrease in autophagy and the accumulation of proteins. In fact, simply increasing eIF2β levels was enough to impair autophagy and cause problems with neuronal function.
Crucially, the researchers found that by reducing the levels of eIF2β, they could restore the cellular recycling process and improve neuronal function even when axonal mitochondria were depleted. This suggests a vital connection, or “axis,” between mitochondria and eIF2β in maintaining the delicate balance of proteins, known as proteostasis, within axons as we age. Disruptions in this axis could be a fundamental factor in the onset and progression of age-related neurodegenerative diseases. Understanding this mechanism opens new avenues for exploring potential therapeutic strategies to combat brain aging.
Source: link to paper