Mitochondria in the nervous system: From health to disease, part II
Introduction
Because of their physical and functional association with crucial pathways in energy metabolism, mitochondria are classically considered the “powerhouse of the cell”. Following studies on a number of mitochondria-linked human diseases, our modern view of these organelles has evolved and expanded, assigning them a plethora of other functions regulating the life and death of a cell, be it in differentiation and development or in ageing and disease. This second volume of the Special Issue on “Mitochondria in the Nervous System: From Health to Disease” brings together 17 articles, with some covering aspects of basic mitochondrial function and dynamics, and others focusing on the role played by alterations of these organelles in neurological diseases. Such alterations might constitute a target for therapy, provided that we first succeed in fully elucidating how the complex mitochondrial molecular network is regulated.
Section snippets
Physiological mitochondrial functions in the CNS
Christos Chinopoulos (Chinopoulos 2017) opens this issue with a critical review on what we know - or thought we knew - on the structure of the mitochondrial permeability transition (mPT) pore. The mPT pore is a megachannel of the inner mitochondrial membrane allowing a non-selective flux of metabolites with a molecular weight of up to 1.5 kDa (Crompton, 1999). Its prolonged opening leads to severe mitochondrial impairment causing cell death in a final pathway that is common to major disease
Mitochondrial dynamics
Over the last fifteen years, a number of studies have revolutionized the classical view of mitochondria as “static” cell components. These organelles undergo a dynamic control of their shape through the regulation of proteins dictating their fusion or fission, but also undergo degradation through a specific autophagic modality named mitophagy.
In this Issue, Rodolfo et al. briefly review current evidence supporting a central role for the ubiquitin-proteasome, autophagy and mitophagy pathways in
Mitochondrial pathology
Because of their many crucial functions in cell physiology, it is not surprising that mitochondrial proteins are involved in or mediate a number of different human diseases. For instance, Drp1 deficiency has been associated with autosomal recessive spastic ataxia of Charlevoix Saguenay, one of the major forms of human mitochondrial ataxia that is associated with increased mitochondrial size, mitochondrial dysfunction and degeneration of Purkinje neurons (Girard et al., 2012). Because of their
Mitochondrial therapy
From what is summarized above, it is clear that some kind of “mitochondrial therapy” seems a promising approach in a number of neurological conditions. This concept is further stressed in the paper by Koppel et al., reviewing current evidence that neuroketotherapeutics, i.e. interventions that serve to produce or introduce ketone bodies, and thus induce ketosis, provide neurologic benefits. These benefits appear to occur not only by enhancing mitochondrial respiration, but also by attenuating
Conclusion
Mitochondrial dysfunction due to impairment of proteins encoded by both nuclear and mitochondrial genes has been linked to more than 400 human diseases, including a large group of neurodegenerative disorders (Nunnari and Suomalainen, 2012). The increasing interest in neuro-mitopathologies is promoting basic and clinical research, as outlined in the 17 articles included in Part II of this Special Issue. Recent advances in technology (e.g. the CRISPR/Cas9 targeted genome editing, or optogenetics,
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