Abstract
Accumulating evidence indicates that dysfunction of mitochondria is a common feature of Parkinson disease. Functional loss of a familial Parkinson disease-linked gene, BRPK/PINK1 (PINK1), results in deterioration of mitochondrial functions and eventual neuronal cell death. A mitochondrial chaperone protein has been shown to be a substrate of PINK1 kinase activity. In this study, we demonstrated that PINK1 has another action point in the cytoplasm. Phosphorylation of Akt at Ser-473 was enhanced by overexpression of PINK1, and the Akt activation was crucial for protection of SH-SY5Y cells from various cytotoxic agents, including oxidative stress. Enhanced Akt phosphorylation was not due to activation of phosphatidylinositol 3-kinase but due to activation of mammalian target of rapamycin complex 2 (mTORC2) by PINK1. Rictor, a specific component of mTORC2, was phosphorylated by overexpression of PINK1. Furthermore, overexpression of PINK1 enhanced cell motility. These results indicate that PINK1 exerts its cytoprotective function not only in mitochondria but also in the cytoplasm through activation of mTORC2.
| Original language | English |
|---|---|
| Pages (from-to) | 7182-7189 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 286 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Mar 4 2011 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
A new cytosolic pathway from a Parkinson disease-associated kinase, BRPK/PINK1 : Activation of AKT via MTORC2. / Murata, Hitoshi; Sakaguchi, Masakiyo; Jin, Yu; Sakaguchi, Yoshihiko; Futami, Junichiro; Yamada, Hidenori; Kataoka, Ken; Huh, Nam Ho.
In: Journal of Biological Chemistry, Vol. 286, No. 9, 04.03.2011, p. 7182-7189.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A new cytosolic pathway from a Parkinson disease-associated kinase, BRPK/PINK1
T2 - Activation of AKT via MTORC2
AU - Murata, Hitoshi
AU - Sakaguchi, Masakiyo
AU - Jin, Yu
AU - Sakaguchi, Yoshihiko
AU - Futami, Junichiro
AU - Yamada, Hidenori
AU - Kataoka, Ken
AU - Huh, Nam Ho
PY - 2011/3/4
Y1 - 2011/3/4
N2 - Accumulating evidence indicates that dysfunction of mitochondria is a common feature of Parkinson disease. Functional loss of a familial Parkinson disease-linked gene, BRPK/PINK1 (PINK1), results in deterioration of mitochondrial functions and eventual neuronal cell death. A mitochondrial chaperone protein has been shown to be a substrate of PINK1 kinase activity. In this study, we demonstrated that PINK1 has another action point in the cytoplasm. Phosphorylation of Akt at Ser-473 was enhanced by overexpression of PINK1, and the Akt activation was crucial for protection of SH-SY5Y cells from various cytotoxic agents, including oxidative stress. Enhanced Akt phosphorylation was not due to activation of phosphatidylinositol 3-kinase but due to activation of mammalian target of rapamycin complex 2 (mTORC2) by PINK1. Rictor, a specific component of mTORC2, was phosphorylated by overexpression of PINK1. Furthermore, overexpression of PINK1 enhanced cell motility. These results indicate that PINK1 exerts its cytoprotective function not only in mitochondria but also in the cytoplasm through activation of mTORC2.
AB - Accumulating evidence indicates that dysfunction of mitochondria is a common feature of Parkinson disease. Functional loss of a familial Parkinson disease-linked gene, BRPK/PINK1 (PINK1), results in deterioration of mitochondrial functions and eventual neuronal cell death. A mitochondrial chaperone protein has been shown to be a substrate of PINK1 kinase activity. In this study, we demonstrated that PINK1 has another action point in the cytoplasm. Phosphorylation of Akt at Ser-473 was enhanced by overexpression of PINK1, and the Akt activation was crucial for protection of SH-SY5Y cells from various cytotoxic agents, including oxidative stress. Enhanced Akt phosphorylation was not due to activation of phosphatidylinositol 3-kinase but due to activation of mammalian target of rapamycin complex 2 (mTORC2) by PINK1. Rictor, a specific component of mTORC2, was phosphorylated by overexpression of PINK1. Furthermore, overexpression of PINK1 enhanced cell motility. These results indicate that PINK1 exerts its cytoprotective function not only in mitochondria but also in the cytoplasm through activation of mTORC2.
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U2 - 10.1074/jbc.M110.179390
DO - 10.1074/jbc.M110.179390
M3 - Article
C2 - 21177249
AN - SCOPUS:79953185407
VL - 286
SP - 7182
EP - 7189
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 9
ER -