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A hyperfused mitochondrial state achieved at G1-S regulates cyclin E buildup and entry into S phase
被引:480
作者:
Mitra, Kasturi
[1
]
Wunder, Christian
[1
]
Roysam, Badrinath
[2
]
Lin, Gang
[2
]
Lippincott-Schwartz, Jennifer
[1
]
机构:
[1] NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA
[2] Rensselaer Polytech Inst, Dept Elect Comp & Syst Engn, Troy, NY 12180 USA
来源:
基金:
美国国家科学基金会;
美国国家卫生研究院;
关键词:
cell cycle;
mitochondrial morphology;
dynamin-related protein 1;
CELL-CYCLE;
LIVING CELLS;
PROGRESSION;
DYNAMICS;
P53;
MORPHOLOGY;
APOPTOSIS;
MULTIPLE;
FUSION;
D O I:
10.1073/pnas.0904875106
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Mitochondria undergo fission-fusion events that render these organelles highly dynamic in cells. We report a relationship between mitochondrial form and cell cycle control at the G(1)-S boundary. Mitochondria convert from isolated, fragmented elements into a hyperfused, giant network at G(1)-S transition. The network is electrically continuous and has greater ATP output than mitochondria at any other cell cycle stage. Depolarizing mitochondria at early G(1) to prevent these changes causes cell cycle progression into S phase to be blocked. Inducing mitochondrial hyperfusion by acute inhibition of dynamin-related protein-1 (DRP1) causes quiescent cells maintained without growth factors to begin replicating their DNA and coincides with buildup of cyclin E, the cyclin responsible for G(1)-to-S phase progression. Prolonged or untimely formation of hyperfused mitochondria, through chronic inhibition of DRP1, causes defects in mitotic chromosome alignment and S-phase entry characteristic of cyclin E overexpression. These findings suggest a hyperfused mitochondrial system with specialized properties at G(1)-S is linked to cyclin E buildup for regulation of G(1)-to-S progression.
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页码:11960 / 11965
页数:6
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