A comprehensive assessment of mitochondrial protein synthesis and cellular proliferation with age and caloric restriction.
A comprehensive assessment of mitochondrial protein synthesis and cellular proliferation with age and caloric restriction.
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DOI：
10.1111/j.1474-9726.2011.00769.x
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发表时间：
2012-02
期刊：
影响因子：
7.8
通讯作者：
Hamilton KL
中科院分区：
文献类型：
--
作者：
Miller BF;Robinson MM;Bruss MD;Hellerstein M;Hamilton KL
有人提出热量限制（CR）会增加线粒体的生物合成。然而，目前尚不清楚为什么 CR 会增加能源消耗巨大的生物合成过程。我们假设 40% CR 会减少线粒体蛋白质合成，并受到翻译机制而非转录机制的调节。我们评估了年轻（6 个月）、中年（12 个月）和老年（24 个月）雄性 B6D2F1 小鼠（作为终生 CR 或随意 (AL) 对照）的 6 周内累积的线粒体蛋白合成及其在肝脏、心脏和骨骼肌中的转录和翻译调节。 AL 和 CR 之间的线粒体蛋白质合成没有差异（6 周内的合成分数（范围）：肝脏 91 – 100%，心脏 74–85%，骨骼肌 53–72%），尽管 CR 时肝脏和心脏的细胞增殖减少。 CR 后，心脏和肝脏中 AMP 激活蛋白激酶 (AMPK) 磷酸化：总磷酸化 (P:T) 增加，所有组织中过氧化物酶体增殖物激活受体 γ 共激活剂 1-α (PGC-1α) mRNA 增加，但蛋白质不增加。核糖体蛋白 S6 (RpS6) 随 CR 减少。总之，CR 维持线粒体蛋白质合成，同时在能量应激期间减少细胞增殖，这与 CR 增加体细胞维持的概念是一致的。全局翻译起始的替代机制可能负责线粒体蛋白的选择性翻译。
It is proposed that caloric restriction (CR) increases mitochondrial biogenesis. However, it is not clear why CR increases an energetically costly biosynthetic process. We hypothesized that 40% CR would decrease mitochondrial protein synthesis and would be regulated by translational rather than transcriptional mechanisms. We assessed cumulative mitochondrial protein synthesis over 6 weeks and its transcriptional and translational regulation in the liver, heart, and skeletal muscle of young (6 mo), middle (12 mo), and old (24 mo) male B6D2F1 mice that were lifelong CR or ad lib (AL) controls. Mitochondrial protein synthesis was not different between AL and CR (Fractional synthesis over 6-weeks (range): liver 91 – 100%, heart 74–85% skeletal muscle 53–72%) despite a decreased cellular proliferation in liver and heart with CR. With CR there was an increase in AMP activated protein kinase (AMPK) phosphorylation:total (P:T) in heart and liver, and an increase in peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) mRNA in all tissues, but not protein. Ribosomal protein S6 (RpS6) was decreased with CR. In conclusion, CR maintained mitochondrial protein synthesis while decreasing cellular proliferation during a time of energetic stress, which is consistent with the concept that CR increases somatic maintenance. Alternative mechanisms to global translation initiation may be responsible for selective translation of mitochondrial proteins.
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影响因子：
15.8
作者：
Civitarese AE;Carling S;Heilbronn LK;Hulver MH;Ukropcova B;Deutsch WA;Smith SR;Ravussin E;CALERIE Pennington Team
通讯作者：
CALERIE Pennington Team
影响因子：
4.8
作者：
Hancock, Chad R.;Han, Dong-Ho;Holloszy, John O.
通讯作者：
Holloszy, John O.
DOI：
10.1073/pnas.232551499
发表时间：
2002-11-26
影响因子：
11.1
作者：
Neese, RA;Misell, LM;Hellerstein, MK
通讯作者：
Hellerstein, MK
影响因子：
2.7
作者：
Day, Kenneth;Shefer, Gabi;Yablonka-Reuveni, Zipora
通讯作者：
Yablonka-Reuveni, Zipora
DOI：
10.1016/j.bbagen.2005.12.023
发表时间：
2006-05-01
影响因子：
3
作者：
Busch, Robert;Kim, Yoo-Kyeong;Hellerstein, Marc K.
通讯作者：
Hellerstein, Marc K.