A cold-stress-inducible PERK/OGT axis controls TOM70-assisted mitochondrial protein import and cristae formation.
A cold-stress-inducible PERK/OGT axis controls TOM70-assisted mitochondrial protein import and cristae formation.
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DOI：
10.1016/j.cmet.2021.01.013
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发表时间：
2021-03-02
期刊：
影响因子：
29
通讯作者：
Puigserver P
中科院分区：
文献类型：
--
作者：
Latorre-Muro P;O'Malley KE;Bennett CF;Perry EA;Balsa E;Tavares CDJ;Jedrychowski M;Gygi SP;Puigserver P
The architecture of cristae provides a spatial mitochondrial organization that contains functional respiratory complexes. Several protein components including OPA1 and MICOS complex subunits organize cristae structure, but upstream regulatory mechanisms are largely unknown. Here, in vivo and in vitro reconstitution experiments show that the ER kinase PERK promotes cristae formation by increasing TOM70-assisted mitochondrial import of MIC19, a critical subunit of the MICOS complex. Cold stress or β-adrenergic stimulation activates PERK that phosphorylates OGT. Phosphorylated OGT glycosylates TOM70 on Ser94 enhancing MIC19 protein import into mitochondria and promoting cristae formation and respiration. In addition, PERK-activated OGT O-GlcNAcylates and attenuates CK2α activity, which mediates TOM70 Ser94 phosphorylation and decreases MIC19 mitochondrial protein import. We have identified a cold stress inter-organelle PERK-OGT-TOM70 axis that increases cell respiration through mitochondrial protein import and subsequent cristae formation. These studies have significant implications in cellular bioenergetics and adaptations to stress conditions. Latorre-Muro et al. show that a cold-induced PERK/OGT signaling sustains thermogenesis and promotes beige adipose formation. PERK/OGT signals to the mitochondrial outer membrane receptor TOM70 through glycosylation increasing MIC19 protein import. Translocated MIC19 incorporates into the MICOS complex promoting cristae biogenesis and respiration during cold and adrenergic responses.
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DOI：
10.1083/jcb.201708044
发表时间：
2018-04-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Backes S;Hess S;Boos F;Woellhaf MW;Gödel S;Jung M;Mühlhaus T;Herrmann JM
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Herrmann JM
影响因子：
29
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Zeviani M
影响因子：
3.3
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Young, Jason C.
ChChd3 是一种线粒体内膜蛋白，对于维持嵴完整性和线粒体功能至关重要。
DOI：
10.1074/jbc.m110.171975
发表时间：
2011-01-28
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Darshi M;Mendiola VL;Mackey MR;Murphy AN;Koller A;Perkins GA;Ellisman MH;Taylor SS
通讯作者：
Taylor SS
DOI：
10.1152/ajpcell.2000.279.5.c1393
发表时间：
2000-11-01
影响因子：
5.5
作者：
Grey, JY;Connor, MK;Hood, DA
通讯作者：
Hood, DA