Article

Mitochondrial Disorders in the Nervous System

Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
Annual Review of Neuroscience (Impact Factor: 22.66). 02/2008; 31(1):91-123. DOI: 10.1146/annurev.neuro.30.051606.094302
Source: PubMed

ABSTRACT Mitochondrial diseases (encephalomyopathies) have traditionally been ascribed to defects of the respiratory chain, which has helped researchers explain their genetic and clinical complexity. However, other mitochondrial functions are greatly important for the nervous system, including protein importation, organellar dynamics, and programmed cell death. Defects in genes controlling these functions are attracting increasing attention as causes not only of neurological (and psychiatric) diseases but also of age-related neurodegenerative disorders. After discussing some pathogenic conundrums regarding the neurological manifestations of the respiratory chain defects, we review altered mitochondrial dynamics in the etiology of specific neurological diseases and in the physiopathology of more common neurodegenerative disorders.

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    • "A rendszer sérülésével tehát nagy valószínűséggel elégtelenné válik a IV-es respirációs komplex felépítésében és egy sor, eddig ismeretlen mitokondriális folyamatban szerepet játszó fehérje IMS-be, illetve mátrixba irányuló transzportja [30]. A mitokondriális rendellenességek pedig tipikusan a nagy energia-(ATP-) igényű szöveteket, az idegrendszert és a vázizomzatot érintő tünetekkel manifesztálódnak [33]. "
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    • "Although HD is a Mendelian dominant disorder, and the mutation is fully penetrant and predictive, other above-mentioned genetic markers vary widely in the degrees to which they contribute to disease in various patients. Psychiatrists could also order other GTs for medical conditions that can cause psychiatric symptoms, such as mitochondrial disorders, porphyria, and other monogenic disorders (Dimauro and Schon, 2008; Simon and Herkes, 2011). Genetic markers associated with psychiatric pharmacogenomics are also being sought, identified, and used. "
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    • "It has been suggested that when the mitochondrial potential is lost, PINK1 is stabilized (Jin et al., 2010; Narendra et al., 2010) and is able to phosphorylate Parkin at serine 65 (Shiba-Fukushima et al., 2012) and to recruit Parkin onto the mitochondria, where it ubiquitinates a number of mitochondrial membrane proteins, leading to the recruitment of p62 (Geisler et al., 2010) and ULK1 (Mizushima , 2010) to carry out mitophagy. Defects in mitophagy can lead to the accumulation of dysfunctional mitochondria, which is a characteristic of aging-related diseases (Chan, 2006; DiMauro and Schon, 2008; Palikaras and Tavernarakis, 2012) (such as heart failure, Alzheimer disease, and Parkinson disease) and cancers (Kim et al., 2011). Thus, deciphering the regulatory mechanism of mitophagy holds promise for fighting these currently incurable diseases. "
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