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Decreased Mitochondrial Membrane Potential Activates the Mitochondrial Unfolded Protein Response.

Brandon J Berry, Tyrone O Nieves, Andrew P Wojtovich,

Mitochondria are ATP-producing organelles that also signal throughout the cell. Mitochondrial protein homeostasis is regulated through membrane potential-dependent protein import and quality control signaling. The mitochondrial unfolded protein response (UPR<sup>mt</sup>) is a specific program that responds to imbalances in nuclear and mitochondrial gene expression. Mounting evidence suggests that the electrochemical ... Read more >>

MicroPubl Biol (microPublication biology)
[2021, 2021:]

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Over-expression of the constitutive AMPylase FIC-1(E274G) does not deplete cellular ATP pools in C. elegans.

Margaret Champion, Matthias C Truttmann,

Protein AMPylation has emerged as a posttranslational protein modification regulating cellular proteostasis. AMPylation is conferred by Fic AMPylases, which catalyze the covalent attachment of AMP to target proteins at the expense of ATP. Over-expression of constitutive-active Fic AMPylases is toxic. Here, we test the hypothesis that excessive Fic AMPylase activity ... Read more >>

MicroPubl Biol (microPublication biology)
[2021, 2021:]

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Individual point mutations in two ERAD E2 ubiquitin-conjugating enzymes do not affect Caenorhabditis elegans spontaneous reversal frequency.

Mackenzi Oswald, Heino Hulsey-Vincent, Caroline Lina Dahlberg,

MicroPubl Biol (microPublication biology)
[2020, 2020:]

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Mutations in two ERAD E3 ubiquitin ligase enzymes reduce spontaneous reversal frequency in Caenorhabditis elegans.

Mackenzi Oswald, Heino Hulsey-Vincent, Caroline Lina Dahlberg,

MicroPubl Biol (microPublication biology)
[2020, 2020:]

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Glucose concentration does not affect degradation of a protein that aberrantly engages the endoplasmic reticulum translocon.

Courtney L Broshar, Eric M Rubenstein,

MicroPubl Biol (microPublication biology)
[2020, 2020:]

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DNMT1-dependent regulation of cortical interneuron function and survival.

Daniel Pensold, Geraldine Zimmer-Bensch,

Neural Regen Res (Neural regeneration research)
[2021, 16(12):2405-2406]

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dCubilin- or dAMN-mediated protein reabsorption in Drosophila nephrocytes modulates longevity.

Xiaoming Feng, Xizhen Hong, Qiuxia Fan, Liting Chen, Jing Li, Juan Deng, Siqiao Gong, Fan Fan Hou, Fujian Zhang,

Aging is a multifaceted process regulated by multiple cellular pathways, including the proteostasis network. Pharmacological or genetic enhancement of the intracellular proteostasis network extends lifespan and prevents age-related diseases. However, how proteostasis is regulated in different tissues throughout the aging process remains unclear. Here, we show that Drosophila homologs of ... Read more >>

Dis Model Mech (Disease models & mechanisms)
[2021, 14(9):]

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The role of mTOR in age-related diseases.

Zofia Chrienova, Eugenie Nepovimova, Kamil Kuca,

The ageing population is becoming a significant socio-economic issue. To address the expanding health gap, it is important to deepen our understanding of the mechanisms underlying ageing in various organisms at the single-cell level. The discovery of the antifungal, immunosuppressive, and anticancer drug rapamycin, which possesses the ability to extend ... Read more >>

J Enzyme Inhib Med Chem (Journal of enzyme inhibition and medicinal chemistry)
[2021, 36(1):1679-1693]

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Expanding the Family of Extracellular Chaperones: Identification of Human Plasma Proteins with Chaperone Activity.

Nicholas J Geraghty, Sandeep Satapathy, Megan Kelly, Flora Cheng, Albert Lee, Mark R Wilson,

Proteostasis, the balance of protein synthesis, folding and degradation, is essential to maintain cellular function and viability, and the many known intracellular chaperones are recognised as playing key roles in sustaining life. In contrast, the identity of constitutively secreted extracellular chaperones (ECs) and their physiological roles in extracellular proteostasis is ... Read more >>

Protein Sci (Protein science : a publication of the Protein Society)
[2021, :]

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Distinct proteostasis states drive pharmacologic chaperone susceptibility for Cystic Fibrosis Transmembrane Conductance Regulator misfolding mutants

Eli Fritz McDonald, Carleen Mae Sabusap, Minsoo Kim, Lars Plate,

<h4>ABSTRACT</h4> Pharmacological chaperones represent a class of therapeutic compounds for treating protein misfolding diseases. One of the most prominent examples is the FDA-approved pharmacological chaperone lumacaftor (VX-809), which has transformed cystic fibrosis (CF) therapy. CF is a fatal disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). ... Read more >>

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Fluc-EGFP reporter mice reveal differential alterations of neuronal proteostasis in aging and disease.

Sonja Blumenstock, Elena Katharina Schulz-Trieglaff, Kerstin Voelkl, Anna-Lena Bolender, Paul Lapios, Jana Lindner, Mark S Hipp, F Ulrich Hartl, Rüdiger Klein, Irina Dudanova,

The cellular protein quality control machinery is important for preventing protein misfolding and aggregation. Declining protein homeostasis (proteostasis) is believed to play a crucial role in age-related neurodegenerative disorders. However, how neuronal proteostasis capacity changes in different diseases is not yet sufficiently understood, and progress in this area has been ... Read more >>

EMBO J (The EMBO journal)
[2021, :e107260]

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Genetically-Determined Myb Insufficiency Directly Impacts on Proteostasis in Hematopoietic Stem Cells Predisposing to Age-Related Myeloid Neoplasia

M.L. Clarke, R.B. Lemma, D.S. Walton, Volpe, Noyvert, O.S. Gabrielsen, Frampton,

<h4>SUMMARY</h4> Acquired disturbances of signaling components in hematopoietic stem cells (HSC) are a feature of hematological neoplasia. Such driver mutations often require additional genetic or environmental influences to elicit transformation. Gene association studies reveal that some of these influences are natural inherited variants. Acquired genetic dysregulation of Myb, which plays ... Read more >>

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Endogenous dipeptide-carnosine supplementation ameliorates hypobaric hypoxia-induced skeletal muscle loss via attenuating endoplasmic reticulum stress response and maintaining proteostasis.

Akanksha Agrawal, Richa Rathor, Ravi Kumar, Som Nath Singh, Bhuvnesh Kumar, Geetha Suryakumar,

High altitude is an environmental stress that is accompanied with numerous adverse biological responses, including skeletal muscle weakness and muscle protein loss. Skeletal muscle wasting is an important clinical problem, progressing to critical illness, associated with increased morbidity and mortality. The present study explores the protective efficacy of endogenous dipeptide, ... Read more >>

IUBMB Life (IUBMB life)
[2021, :]

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Editorial: Post-translational Modifications and Compartmentalized Protein Quality Control in Cardiac Muscle and Disease.

Mark J Ranek, Aldrin V Gomes, Huabo Su,

Front Physiol (Frontiers in physiology)
[2021, 12:745887]

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Neural functions of small heat shock proteins.

Teresa de Los Reyes, Sergio Casas-Tintó,

Stress response is a cellular widespread mechanism encoded by a common protein program composed by multiple cellular factors that converge in a defense reaction to protect the cell against damage. Among many mechanisms described, heat shock proteins were proposed as universally conserved protective factors in the stress core proteome, coping ... Read more >>

Neural Regen Res (Neural regeneration research)
[2022, 17(3):512-515]

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Hsf1 promotes hematopoietic stem cell fitness and proteostasis in response to ex vivo culture stress and aging.

Miriama Kruta, Mary Jean Sunshine, Bernadette A Chua, Yunpeng Fu, Ashu Chawla, Christopher H Dillingham, Lorena Hidalgo San Jose, Bijou De Jong, Fanny J Zhou, Robert A J Signer,

Maintaining proteostasis is key to resisting stress and promoting healthy aging. Proteostasis is necessary to preserve stem cell function, but little is known about the mechanisms that regulate proteostasis during stress in stem cells, and whether disruptions of proteostasis contribute to stem cell aging is largely unexplored. We determined that ... Read more >>

Cell Stem Cell (Cell stem cell)
[2021, :]

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Universal protein misfolding intermediates can bypass the proteostasis network and remain soluble and non-functional

Daniel Nissley, Yang Jiang, Fabio Trovato, Ian Sitarik, Karthik Narayan, Edward O’Brien,

<h4>ABSTRACT</h4> Misfolded protein conformations with decreased functionality can bypass the proteostasis machinery and remain soluble in vivo . This is an unexpected phenomenon as several cellular quality control mechanisms have evolved to rid cells of misfolded proteins. Three questions, then, are: how is it structurally possible for long-lived, soluble, misfolded ... Read more >>

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Hsp40 Affinity to Identify Proteins Destabilized by Cellular Toxicant Exposure

Guy Quanrud, Maureen Montoya, Liangyong Mei, Mohammad Awad, Joseph Genereux,

Environmental toxins and toxicants can damage proteins and threaten cellular proteostasis. Most current methodologies to identify misfolded proteins in cells survey the entire proteome for sites of changed reactivity. We describe and apply a quantitative proteomics methodology to identify destabilized proteins based on their binding to the human Hsp40 chaperone ... Read more >>

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Increased mitochondrial calcium uptake and concomitant mitochondrial activity by presenilin loss promotes mTORC1 signaling to drive neurodegeneration.

Kerry C Ryan, Zahra Ashkavand, Shaarika Sarasija, Jocelyn T Laboy, Rohan Samarakoon, Kenneth R Norman,

Metabolic dysfunction and protein aggregation are common characteristics that occur in age-related neurodegenerative disease. However, the mechanisms underlying these abnormalities remain poorly understood. We have found that mutations in the gene encoding presenilin in Caenorhabditis elegans, sel-12, results in elevated mitochondrial activity that drives oxidative stress and neuronal dysfunction. Mutations ... Read more >>

Aging Cell (Aging cell)
[2021, :e13472]

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Crotamiton derivative JM03 extends lifespan and improves oxidative and hypertonic stress resistance in Caenorhabditis elegans via inhibiting OSM-9

Keting Bao, Jiali Feng, Wenwen Liu, Zhifan Mao, Lingyuan Bao, Tianyue Sun, Zhouzhi Song, Zelan Hu, Jian Li,

While screening our in-house 1,072 marketed drugs for their ability to extend the lifespan using Caenorhabditis elegans ( C. elegans ) as an animal model, crotamiton ( N -ethyl-o-crotonotoluidide) showed anti-aging activity and was selected for further structural optimization. After replacing the ortho-methyl of crotamiton with ortho-fluoro, crotamiton derivative JM03 ... Read more >>

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Increased fidelity of protein synthesis extends lifespan.

Victoria Eugenia Martinez-Miguel, Celia Lujan, Tristan Espie-Caullet, Daniel Martinez-Martinez, Saul Moore, Cassandra Backes, Suam Gonzalez, Evgeniy R Galimov, André E X Brown, Mario Halic, Kazunori Tomita, Charalampos Rallis, Tobias von der Haar, Filipe Cabreiro, Ivana Bjedov,

Loss of proteostasis is a fundamental process driving aging. Proteostasis is affected by the accuracy of translation, yet the physiological consequence of having fewer protein synthesis errors during multi-cellular organismal aging is poorly understood. Our phylogenetic analysis of RPS23, a key protein in the ribosomal decoding center, uncovered a lysine ... Read more >>

Cell Metab (Cell metabolism)
[2021, :]

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A role for mitochondrial DNA in cellular proteostasis.

Caroline Barranco,

Nat Rev Genet (Nature reviews. Genetics)
[2021, :]

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Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease.

Julia Sánchez-Ceinos, Rocío Guzmán-Ruiz, Oriol Alberto Rangel-Zuñiga, Jaime López-Alcalá, Elena Moreno-Caño, Mercedes Del Río-Moreno, Juan Luis Romero-Cabrera, Pablo Pérez-Martínez, Elsa Maymo-Masip, Joan Vendrell, Sonia Fernández-Veledo, José Manuel Fernández-Real, Jurga Laurencikiene, Mikael Rydén, Antonio Membrives, Raul M Luque, José López-Miranda, María M Malagón,

Preadipocytes are crucial for healthy adipose tissue expansion. Preadipocyte differentiation is altered in obese individuals, which has been proposed to contribute to obesity-associated metabolic disturbances. Here, we aimed at identifying the pathogenic processes underlying impaired adipocyte differentiation in obese individuals with insulin resistance (IR)/type 2 diabetes (T2D). We report that ... Read more >>

Elife (eLife)
[2021, 10:]

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The Proteome Folding Problem and Cellular Proteostasis.

Evan T Powers, Lila M Gierasch,

Stunning advances have been achieved in addressing the protein folding problem, providing deeper understanding of the mechanisms by which proteins navigate energy landscapes to reach their native states and enabling powerful algorithms to connect sequence to structure. However, the realities of the in vivo protein folding problem remain a challenge ... Read more >>

J Mol Biol (Journal of molecular biology)
[2021, :167197]

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Myocardial protein aggregates in pet guinea pigs.

Teresa Southard, Kathleen Kelly, Anibal G Armien,

A retrospective study of guinea pigs submitted for necropsy revealed intracytoplasmic inclusions in the cardiomyocytes of 26 of 30 animals. The inclusions were found with approximately the same frequency in male and female guinea pigs and were slightly more common in older animals. In most cases, the animals did not ... Read more >>

Vet Pathol (Veterinary pathology)
[2021, :3009858211042586]

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