A Conserved Mito-Cytosolic Translational Balance Links Two Longevity Pathways

被引：83

作者：

Molenaars, Marte ^{[1
]}

Janssens, Georges E. ^{[1
]}

Williams, Evan G. ^{[2
]}

Jongejan, Aldo ^{[3
]}

Lan, Jiayi ^{[2
]}

Rabot, Sylvie ^{[4
]}

Joly, Fatima ^{[4
]}

Moerland, Perry D. ^{[3
]}

Schomakers, Bauke, V ^{[1
,5
]}

Lezzerini, Marco ^{[1
]}

Liu, Yasmine J. ^{[1
]}

McCormick, Mark A. ^{[6
,7
]}

Kennedy, Brian K. ^{[8
,9
]}

van Weeghel, Michel ^{[1
,5
]}

van Kampen, Antoine H. C. ^{[3
]}

Aebersold, Ruedi ^{[2
,10
]}

MacInnes, Alyson W. ^{[1
]}

Houtkooper, Riekelt H. ^{[1
]}

机构：

[1] Univ Amsterdam, Lab Genet Metab Dis, Amsterdam Gastroenterol & Metab, Amsterdam Cardiovasc Sci,Amsterdam UMC, Amsterdam, Netherlands

[2] Swiss Fed Inst Technol, Inst Mol Syst Biol, Zurich, Switzerland

[3] Univ Amsterdam, Bioinformat Lab, Amsterdam UMC, Amsterdam, Netherlands

[4] Univ Paris Saclay, Micalis Inst, AgroParisTech, INRA, Jouy En Josas, France

[5] Univ Amsterdam, Amsterdam UMC, Core Facil Metabol, Amsterdam, Netherlands

[6] Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA

[7] Univ New Mexico, Hlth Sci Ctr, Autophagy Inflammat & Metab Ctr Biol Res Excellen, Albuquerque, NM 87131 USA

[8] Buck Inst Res Aging, Novato, CA USA

[9] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem & Physiol, Singapore, Singapore

[10] Univ Zurich, Fac Sci, Zurich, Switzerland

来源：

CELL METABOLISM | 2020年 / 31卷 / 03期

关键词：

MESSENGER-RNA TRANSLATION; ATP-CONSUMING PROCESSES; EXTENDS LIFE-SPAN; MITOCHONDRIAL PROTEINS; SIGNALING PATHWAY; GENE-EXPRESSION; YEAST; TOR; ATF4; INHIBITION;

D O I：

10.1016/j.cmet.2020.01.011

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Slowing down translation in either the cytosol or the mitochondria is a conserved longevity mechanism. Here, we found a non-interventional natural correlation of mitochondrial and cytosolic ribosomal proteins (RPs) in mouse population genetics, suggesting a translational balance. Inhibiting mitochondrial translation in C. elegans through mrps-5 RNAi repressed cytosolic translation. Transcriptomics integrated with proteomics revealed that this inhibition specifically reduced translational efficiency of mRNAs required in growth pathways while increasing stress response mRNAs. The repression of cytosolic translation and extension of lifespan from mrps-5 RNAi were dependent on atf-5/ATF4 and independent from metabolic phenotypes. We found the translational balance to be conserved in mammalian cells upon inhibiting mitochondrial translation pharmacologically with doxycycline. Lastly, extending this in vivo, doxycycline repressed cytosolic translation in the livers of germ-free mice. These data demonstrate that inhibiting mitochondrial translation initiates an atf-5/ATF4-dependent cascade leading to coordinated repression of cytosolic translation, which could be targeted to promote longevity.

引用

页码：549 / +

页数：22

共 1 条

[1] Mito-cytoplasmic translational balance in the regulation of longevity
Molenaars, M.
Janssens, G.
Lan, J.
Jongejan, A.
Moerland, P.
van Kampen, A.
Williams, E.
Aebersold, R.
MacInnes, A.
Houtkooper, R.
FEBS OPEN BIO, 2018, 8 : 92 - 92

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