Controlled and Impaired Mitochondrial Quality in Neurons: Molecular Physiology and Prospective Pharmacology

Tuned mitochondrial physiology is fundamental for qualitative cellular function. This is particularly relevant for neurons, whose pathology is frequently associated with mitochondrial deficiencies. Defects in mitochondria are indeed key features in most neurodegenerative diseases such as Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD) and Amyotrophic Lateral Sclerosis (ALS).When mitochondrial coupling impairs, so does cell metabolism, trafficking and the signaling depending on the homeostasis of the mitochondrial network. Moreover, the quality control of mitochondria - via the process of mitochondrial autophagy - results biased in neurodegeneration stemming major interest on the molecular determinants of this process among neuroscientists.In this review, we highlight the most notable and acknowledged deficiencies of mitochondrial function and their relationship with diseases occurring in neurons and their transmission.The physiological aspects of mitochondrial biology in relation to bio-energy, dynamics and quality control will be discussed with the finality to form a comprehensive picture of the mitochondrial contribution to the pathophysiology of neurodegenerative syndromes. In this way we aim to set the scene to conceive novel strategies to better diagnose and target these debilitative conditions.

Graphical abstractNeurodegenerative conditions are heavily influenced by the quality of mitochondrial function thus focusing the general attention on their physiopathology. The core functional and regulatory aspects of mitochondrial homeostasis and life-cycle are here depicted highlighting the role played in this by the catabolic, finely tuned, processes such as mitochondrial autophagy. The mitochondrial drugs, hitherto known and available, and potentially beneficial for the pharmacological treatment of neurodegenerative conditions are also reported.Download high-res image (127KB)Download full-size image