Faculty Opinions recommendation of An evolutionarily conserved mechanism for controlling the efficiency of protein translation.

Aging research has been very successful at identifying signaling pathways and evolutionarily conserved genes that extend lifespan with the assumption that an increase in lifespan will also increase healthspan. However, it is largely unknown whether we are extending the healthy time of life or simply prolonging a period of frailty with increased incidence of age-associated diseases. Here we use Caenorhabditis elegans, one of the premiere systems for lifespan studies, to determine whether lifespan and healthspan are intrinsically correlated. We conducted multiple cellular and organismal assays on wild type as well as four long-lived mutants (insulin/insulin-like growth factor-1, dietary restriction, protein translation, mitochondrial signaling) in a longitudinal manner to determine the health of the animals as they age. We find that some long-lived mutants performed better than wild type when measured chronologically (number of days). However, all long-lived mutants increased the proportion of time spent in a frail state. Together, these data suggest that lifespan can no longer be the sole parameter of interest and reveal the importance of evaluating multiple healthspan parameters for future studies on antiaging interventions.

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An Evolutionarily Conserved Mechanism for Controlling the Efficiency of Protein Translation

Cell ◽

10.1016/j.cell.2010.03.031 ◽

2010 ◽

Vol 141 (2) ◽

pp. 344-354 ◽

Cited By ~ 519

Author(s):

Tamir Tuller ◽

Asaf Carmi ◽

Kalin Vestsigian ◽

Sivan Navon ◽

Yuval Dorfan ◽

...

Keyword(s):

Protein Translation ◽

Evolutionarily Conserved

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mTor Signaling in Skeletal Muscle During Sepsis and Inflammation: Where Does It All Go Wrong?

Physiology ◽

10.1152/physiol.00044.2010 ◽

2011 ◽

Vol 26 (2) ◽

pp. 83-96 ◽

Cited By ~ 52

Author(s):

Robert A. Frost ◽

Charles H. Lang

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Growth Factors ◽

Protein Metabolism ◽

Muscle Protein ◽

Mammalian Target Of Rapamycin ◽

Protein Translation ◽

Mtor Signaling ◽

Evolutionarily Conserved ◽

Control Protein

The mammalian target of rapamycin (mTOR) is an evolutionarily conserved protein kinase that exquisitely regulates protein metabolism in skeletal muscle. mTOR integrates input from amino acids, growth factors, and intracellular cues to make or break muscle protein. mTOR accomplishes this task by stimulating the phosphorylation of substrates that control protein translation while simultaneously inhibiting proteasomal and autophagic protein degradation. In a metabolic twist of fate, sepsis induces muscle atrophy in part by the aberrant regulation of mTOR. In this review, we track the steps of normal mTOR signaling in muscle and examine where they go astray in sepsis and inflammation.

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Amino Acids Promote Mitochondrial-Derived Compartment Formation in Mammalian Cells

10.1101/2020.12.23.424218 ◽

2020 ◽

Author(s):

Max-Hinderk Schuler ◽

Alyssa M. English ◽

Leah VanderMeer ◽

Janet M. Shaw ◽

Adam L. Hughes

Keyword(s):

Amino Acid ◽

Mammalian Cells ◽

Metabolic Stress ◽

Amino Acid Content ◽

Protein Translation ◽

Translation Inhibition ◽

Evolutionarily Conserved ◽

Amino Acid Levels ◽

Mitochondrial Remodeling ◽

Cellular Stressors

SUMMARYWe recently identified a new cellular structure in yeast, called the Mitochondrial-Derived Compartment (MDC), that forms on mitochondria in response to amino acid excess. While emerging evidence supports an important function for MDCs in protecting cells from metabolic stress, whether this system exists beyond yeast remains unclear. Here, we show that MDCs are conserved in mammals, and like their yeast counterparts, are responsive to the intracellular amino acid content. Specifically, we find that inhibition of protein translation stimulates formation of dynamic, micron-sized compartments that associate with the mitochondrial network. These compartments are enriched for the carrier receptor Tomm70A and other select mitochondrial outer and inner membrane cargo, associate with the ER membrane, and require the conserved GTPase Miro1 for formation. Mammalian MDCs are responsive to changes in amino acid levels during translation inhibition, and are not activated by other common cellular stressors. Thus, MDCs represent an evolutionarily conserved nutrient-responsive mitochondrial remodeling system.

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The Bic-C Family of Developmental Translational Regulators

Comparative and Functional Genomics ◽

10.1155/2012/141386 ◽

2012 ◽

Vol 2012 ◽

pp. 1-23 ◽

Cited By ~ 11

Author(s):

Chiara Gamberi ◽

Paul Lasko

Keyword(s):

Developmental Biology ◽

Human Disease ◽

Rna Binding ◽

Rna Binding Proteins ◽

Mrna Translation ◽

Protein Translation ◽

Model Organisms ◽

Founding Member ◽

Evolutionarily Conserved ◽

Translational Regulators

Regulation of mRNA translation is especially important during cellular and developmental processes. Many evolutionarily conserved proteins act in the context of multiprotein complexes and modulate protein translation both at the spatial and the temporal levels. Among these, Bicaudal C constitutes a family of RNA binding proteins whose founding member was first identified inDrosophilaand contains orthologs in vertebrates. We discuss recent advances towards understanding the functions of these proteins in the context of the cellular and developmental biology of many model organisms and their connection to human disease.

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Apoptosis and development

Essays in Biochemistry ◽

10.1042/bse0390011 ◽

2003 ◽

Vol 39 ◽

pp. 11-24 ◽

Cited By ~ 6

Author(s):

Justin V McCarthy

Keyword(s):

Drosophila Melanogaster ◽

Mammalian Cells ◽

Cell Number ◽

Model Organisms ◽

Biological Processes ◽

Nematode Caenorhabditis Elegans ◽

Apoptotic Pathway ◽

Genetic Pathways ◽

Evolutionarily Conserved ◽

Multicellular Organisms

Apoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The large diversity of regulators of apoptosis in mammalian cells and their numerous interactions complicate the analysis of their individual functions, particularly in development. The remarkable conservation of apoptotic mechanisms across species has allowed the genetic pathways of apoptosis determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, to act as models for understanding the biology of apoptosis in mammalian cells. Though many components of the apoptotic pathway are conserved between species, the use of additional model organisms has revealed several important differences and supports the use of model organisms in deciphering complex biological processes such as apoptosis.

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