Molecular Chaperones

Publication Title: 
Annals of the New York Academy of Sciences

Aging is a complex process accompanied by a decreased capacity of cells to cope with random molecular damages. Damaged proteins can form aggregates and have cytotoxic properties, a feature of many age-associated diseases. Small Hsps are chaperones involved in the refolding and/or disposal of protein aggregates. In Drosophila melanogaster, the mitochondrial DmHsp22 is preferentially upregulated during aging. Its over-expression results in an extension of lifespan (>30%) and an increased resistance to stress.

Author(s): 
Morrow, GeneviËve
Kim, Hyun-Ju
Le PÈcheur, Marie
Kaul, Sunil C.
Wadhwa, Renu
Tanguay, Robert M.
Publication Title: 
Ageing Research Reviews

Autophagy is a lysosomal degradation process that evolved as a starvation response in lower eukaryotes and has gained numerous functions in higher organisms. In animals, autophagy works as a central process in cellular quality control by removing waste or excess proteins and organelles. Impaired autophagy and the age-related decline of this pathway favour the pathogenesis of many diseases that occur especially at higher age such as neurodegenerative diseases and cancer. Caloric restriction (CR) promotes longevity and healthy ageing.

Author(s): 
Pallauf, Kathrin
Rimbach, Gerald
Publication Title: 
Rejuvenation Research

Bile acids are detergent molecules derived from cholesterol in the liver that are important for the metabolism and absorption of lipids in the intestine. Bile acids are also steroid hormones activating specific nuclear receptors and G protein-coupled receptors. Conjugated bile acids are cytoprotective and anticarcinogenic. Bile acid synthesis and bile flow decreases markedly during aging.

Author(s): 
Kr¯ll, Jens
Publication Title: 
Molecular Cell

Cellular processes function through multistep pathways that are reliant on the controlled association and disassociation of sequential protein complexes. While dynamic action is critical to propagate and terminate work, the mechanisms used to disassemble biological structures are not fully understood. Here we show that the p23 molecular chaperone initiates disassembly of protein-DNA complexes and that the GCN5 acetyltransferase prolongs the dissociated state through lysine acetylation.

Author(s): 
Zelin, Elena
Zhang, Yang
Toogun, Oyetunji A.
Zhong, Sheng
Freeman, Brian C.
Publication Title: 
Molecular and Cellular Biology

The AU-rich elements (AREs) encoded within many mRNA 3' untranslated regions (3'UTRs) are targets for factors that control transcript longevity and translational efficiency. Hsp70, best known as a protein chaperone with well-defined peptide-refolding properties, is known to interact with ARE-like RNA substrates in vitro. Here, we show that cofactor-free preparations of Hsp70 form direct, high-affinity complexes with ARE substrates based on specific recognition of U-rich sequences by both the ATP- and peptide-binding domains.

Author(s): 
Kishor, Aparna
Tandukar, Bishal
Ly, Yann V.
Toth, Eric A.
Suarez, Yvelisse
Brewer, Gary
Wilson, Gerald M.
Publication Title: 
Molecular Aspects of Medicine

The SLC16 gene family has fourteen members. Four (SLC16A1, SLC16A3, SLC16A7, and SLC16A8) encode monocarboxylate transporters (MCT1, MCT4, MCT2, and MCT3, respectively) catalysing the proton-linked transport of monocarboxylates such as l-lactate, pyruvate and ketone bodies across the plasma membrane. SLC16A2 encodes a high affinity thyroid hormone transporter (MCT8) and SLC16A10 an aromatic amino acid transporter (TAT1). The substrates and roles of the remaining eight members are unknown.

Author(s): 
Halestrap, Andrew P.
Publication Title: 
PloS One

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons in the spinal cord, brain stem, and motor cortex. Mutations in superoxide dismutase (SOD1) are associated with familial ALS and lead to SOD1 protein misfolding and aggregation. Here we show that the molecular chaperone, HSJ1 (DNAJB2), mutations in which cause distal hereditary motor neuropathy, can reduce mutant SOD1 aggregation and improve motor neuron survival in mutant SOD1 models of ALS.

Author(s): 
Novoselov, Sergey S.
Mustill, Wendy J.
Gray, Anna L.
Dick, James R.
Kanuga, Naheed
Kalmar, Bernadett
Greensmith, Linda
Cheetham, Michael E.
Publication Title: 
Nature

The blood system is sustained by a pool of haematopoietic stem cells (HSCs) that are long-lived due to their capacity for self-renewal. A consequence of longevity is exposure to stress stimuli including reactive oxygen species (ROS), nutrient fluctuation and DNA damage. Damage that occurs within stressed HSCs must be tightly controlled to prevent either loss of function or the clonal persistence of oncogenic mutations that increase the risk of leukaemogenesis.

Author(s): 
van Galen, Peter
Kreso, Antonija
Mbong, Nathan
Kent, David G.
Fitzmaurice, Timothy
Chambers, Joseph E.
Xie, Stephanie
Laurenti, Elisa
Hermans, Karin
Eppert, Kolja
Marciniak, Stefan J.
Goodall, Jane C.
Green, Anthony R.
Wouters, Bradly G.
Wienholds, Erno
Dick, John E.
Publication Title: 
Cell Stress & Chaperones

Chaperone function plays a key role in repairing proteotoxic damage, in the maintenance of cell architecture, and in cell survival. Here, we summarize our current knowledge about changes in chaperone expression and function in the aging process, as well as their involvement in longevity and cellular senescence.

Author(s): 
Soti, Csaba
Csermely, PÈter
Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Author(s): 
Kahn, Arnold J.

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