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Glucocorticoid impairs mitochondrial quality control in neurons.
Choi, Gee Euhn; Han, Ho Jae.
Afiliação
  • Choi GE; Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 Four Future Veterinary Medicine Leading Education & Research Center, Seoul National University, Seoul 08826, Republic of Korea.
  • Han HJ; Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 Four Future Veterinary Medicine Leading Education & Research Center, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: hjhan@snu.ac.kr.
Neurobiol Dis ; 152: 105301, 2021 05.
Article em En | MEDLINE | ID: mdl-33609641
ABSTRACT
Neurons are particularly vulnerable to mitochondrial dysfunction due to high energy demand and an inability to proliferate. Therefore, dysfunctional mitochondria cause various neuropathologies. Mitochondrial damage induces maintenance pathways to repair or eliminate damaged organelles. This mitochondrial quality control (MQC) system maintains appropriate morphology, localization, and removal/replacement of mitochondria to sustain brain homeostasis and counter progression of neurological disorders. Glucocorticoid release is an essential response to stressors for adaptation; however, it often culminates in maladaptation if neurons are exposed to chronic and severe stress. Long-term exposure to high levels of glucocorticoids induces mitochondrial dysfunction via genomic and nongenomic mechanisms. Glucocorticoids induce abnormal mitochondrial morphology and dysregulate fusion and fission. Moreover, mitochondrial trafficking is arrested by glucocorticoids and dysfunctional mitochondria are subsequently accumulated around the soma. These alterations lead to energy deficiency, particularly for synaptic transmission that requires large amounts of energy. Glucocorticoids also impair mitochondrial clearance by preventing mitophagy of damaged organelle and suppress mitochondrial biogenesis, resulting in the reduced number of healthy mitochondria. Failure to maintain MQC degrades brain function and contributes to neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. However, mechanisms of glucocorticoid action on the regulation of MQC during chronic stress conditions are not well understood. The present review discusses pathways involved in the impairment of MQC and the clinical significance of high glucocorticoid blood levels for neurodegenerative diseases.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dinâmica Mitocondrial / Glucocorticoides / Mitocôndrias / Neurônios Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dinâmica Mitocondrial / Glucocorticoides / Mitocôndrias / Neurônios Idioma: En Ano de publicação: 2021 Tipo de documento: Article