SUMO-regulated mitochondrial function in Parkinson's disease.
J Neurochem
; 137(5): 673-86, 2016 06.
Article
em En
| MEDLINE
| ID: mdl-26932327
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by cardinal motor signs such as rigidity, bradykinesia or rest tremor that arise from a significant death of dopaminergic neurons. Non-dopaminergic degeneration also occurs and it seems to induce the deficits in olfactory, emotional, and memory functions that precede the classical motor symptoms in PD. Despite the majority of PD cases being sporadic, several genes have previously been associated with the hereditary forms of the disease. The proteins encoded by some of these genes, including α-synuclein, DJ-1, and parkin, are modified by small ubiquitin-like modifier (SUMO), a post-translational modification that regulates a variety of cellular processes. Among the several pathogenic mechanisms proposed for PD is mitochondrial dysfunction. Recent studies suggest that SUMOylation can interfere with mitochondrial dynamics, which is essential for neuronal function, and may play a pivotal role in PD pathogenesis. Here, we present an overview of recent studies on mitochondrial disturbance in PD and the potential SUMO-modified proteins and pathways involved in this process. SUMOylation, a post-translational modification, interferes with mitochondrial dynamics, and may play a pivotal role in Parkinson's disease (PD). SUMOylation maintains α-synuclein (α-syn) in a soluble form and activates DJ-1, decreasing mitochondrial oxidative stress. SUMOylation may reduce the amount of parkin available for mitochondrial recruitment and decreases mitochondrial biogenesis through suppression of peroxisomal proliferator-activated receptor-γ co-activator 1 α (PGC-1α). Mitochondrial fission can be regulated by dynamin-related protein 1 SUMO-1- or SUMO-2/3-ylation. A fine balance for the SUMOylation/deSUMOylation of these proteins is required to ensure adequate mitochondrial function in PD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina
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Sumoilação
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Mitocôndrias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Reino Unido