title: SUMO-regulated mitochondrial function in Parkinson's disease.
abstract: 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.
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina (UFSC), Campus Trindade, Florianópolis, SC, Brazil.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Guerra de Souza
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina (UFSC), Campus Trindade, Florianópolis, SC, Brazil.
authors.forename: Rui Daniel
authors.initials: RD
authors.lastname: Prediger
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina (UFSC), Campus Trindade, Florianópolis, SC, Brazil.
authors.forename: Helena
authors.initials: H
authors.lastname: Cimarosti
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation / Q000502:physiology*
chemical_list: D025841:Small Ubiquitin-Related Modifier Proteins
keywords: DJ-1; Drp1; PGC-1α; Parkinson's disease; SUMO; mitochondria; parkin; α-synuclein