신경세포 칼슘신호 조절에 있어서의 미토콘드리아의 병태생리적 기능 및 분자기전
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은수용, 정성철 |
제주대학교 의학전문대학원생리학교실 |
Pathophysiological roles and the molecular mechanism of mitochondria in neuronal calcium regulation |
Su- Yong Eun, Sung-Cherl Jung |
Department of Physiology, Jeju National University School of Medicine, Jeju Korea |
Correspondence:
Su- Yong Eun, Email: syeun@jejunu.ac.k |
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Abstract |
Calcium is an important signaling molecule involved in the regulation of many physiological as well as pathological cellular responses. Especially, the spatiotemporal pattern of local calcium signaling is critical for the specificity of cellular responses. We reviewed here pathophysiol0gical roles and the molecular mechanism of mitochondria as well as endoplasmic reticulum (ER) in neuronal calcium regulation. The Iiving cells evoke calcium influx outside the cells and also induce calcium release from ER in response to many stimuli. However, severe and sustained calcium release from ER induces calcium uptake into mitochondria. Pathologically elevated mitochondrial calcium responses are accompanied by mitochondria depolarization. mitochondria permeability transition pore (mtPTP) opining and subsequent mitochondria-dependent apoptosis. Ratiometric realtime measurements of intramitochondrial local Ca suggest that high mitochondrial Ca2+ is the crucial factor determinating whether cells : undergo apoptosis. On the other hand, calcium depletion in ER also induces ER stress which evokes protein folding
defects and ER stress-dependent apoptosis. The recent growing body of evidence on pathophysiological roles and the molecular mechanism of mitochondria as well as ER could provide an insight for the development of new drug to treat neurodegenerative diseases in which pathogenesis either calcium overload or oxidative dative stress is involved. |
Key Words:
Mitochondria; Endoplasmic reticulum; Local calcium; Reactive oxygen species |