Mitochondrial Dynamics and mRNA Translation: A Local Synaptic Tale

Simple Summary Mitochondria-shaping proteins are pivotal in maintaining the dynamic structure of mitochondria, which constantly undergo fusion and fission. This dynamic reshaping is crucial for adapting to the energetic demands of neurons, especially in the axons and dendrites, where mitochondria play vital roles in synaptic activity. Therefore, the precise localization and timely translation of mitochondria-shaping proteins are essential for neuronal resilience and the overall health of the nervous system. Transport granules, which are membrane-less organelles formed through liquid-liquid phase separation, are responsible for transporting these mRNAs. These granules contain RNA-binding proteins (RBPs) that stabilize and regulate mRNA content, ensuring the proper translation of mitochondrial proteins at specific sites. Another mechanism involves tethering mRNAs to organelles such as mitochondria, endosomes, and lysosomes, allowing for rapid and efficient transport in response to cellular signals. Disruptions in these processes can lead to impaired mitochondrial dynamics, contributing to neuronal dysfunction and neurodegenerative diseases such as Alzheimer's and Parkinson's.Abstract Mitochondria are dynamic organelles that can adjust and respond to different stimuli within a cell. This plastic ability allows them to effectively coordinate several cellular functions in cells and becomes particularly relevant in highly complex cells such as neurons. An imbalance in mitochondrial dynamics can disrupt mitochondrial function, leading to abnormal cellular function and ultimately to a range of diseases, including neurodegenerative disorders. Regulation of mRNA transport and local translation inside neurons is crucial for maintaining the proteome of distal mitochondria, which is vital for energy production and synaptic function. A significant portion of the axonal transcriptome is dedicated to mRNAs for mitochondrial proteins, emphasizing the importance of local translation in sustaining mitochondrial function in areas far from the cell body. In neurons, local translation and the regulation of mRNAs encoding mitochondrial-shaping proteins could be essential for synaptic plasticity and neuronal health. The dynamics of these mRNAs, including their transport and local translation, may influence the morphology and function of mitochondria, thereby affecting the overall energy status and responsiveness of synapses. Comprehending the mitochondria-related mRNA regulation and local translation, as well as its influence on mitochondrial morphology near the synapses will help to better understand neuronal physiology and neurological diseases where mitochondrial dysfunction and impaired synaptic plasticity play a central role.