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.
Department of Biology, University of Rome TorVergata, 00133 Rome, Italy.
Ivana
I
Matic
Department of Biology, University of Rome TorVergata, 00133 Rome, Italy.
Daniela
D
Strobbe
RVC Department of Comparative Biomedical Sciences, University of London and UCL Consortium for Mitochondrial Research, Royal College Street NW1 0TU, London, United Kingdom.
Michele
M
Frison
Department of Biology, University of Rome TorVergata, 00133 Rome, Italy; RVC Department of Comparative Biomedical Sciences, University of London and UCL Consortium for Mitochondrial Research, Royal College Street NW1 0TU, London, United Kingdom; Regina Elena-National Cancer Institute, 00144 Rome, Italy. Electronic address: mcampanella@rvc.ac.uk.
Michelangelo
M
Campanella
D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000473:pathology* / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000473:pathology; D009474:Neurons / Q000473:pathology* / Q000502:physiology*
Autophagy; BTB06584 (PubChem CID: 2799764); CoQ10 (PubChem CID: 5281915); Creatine (PubChem CID: 586); Cyclosporine A (PubChem CID: 5284373); MitoQ (PubChem CID: 11388331); Mitochondria; Neurodegeneration; Neurons; PMI (tbc); Vitamin C (PubChem CID: 54670067); Vitamin E (PubChem CID: 2116)