Mitostasis in age-associated neurodegeneration

Abstract

Mitochondria are essential organelles that play crucial roles in various metabolic and signalling pathways. Proper neuronal function is highly dependent on the health of these organelles. Of note, the intricate structure of neurons poses a critical challenge for the transport and distribution of mitochondria to specific energy-intensive domains, such as synapses and dendritic appendages. When faced with chronic metabolic challenges and bioenergetic deficits, neurons undergo degeneration. Unsurprisingly, disruption of mitostasis, the process of maintaining cellular mitochondrial content and function within physiological limits, has been implicated in the pathogenesis of several age-associated neurodegenerative disorders. Indeed, compromised integrity and metabolic activity of mitochondria is a principal hallmark of neurodegeneration. In this review, we survey recent findings elucidating the role of impaired mitochondrial homeostasis and metabolism in the onset and progression of age-related neurodegenerative disorders. We also discuss the importance of neuronal mitostasis, with an emphasis on the major mitochondrial homeostatic and metabolic pathways that contribute to the proper functioning of neurons. A comprehensive delineation of these pathways is crucial for the development of early diagnostic and intervention approaches against neurodegeneration.