Publications de Paolo De Los Rios

Clearing the protein clutter in human cells: the role of protein disaggregases

Cells rely on multiple protein quality control (PQC) pathways, including molecular chaperone-assisted folding and degradation systems, to maintain proteome integrity and functionality. These pathways work together to reduce the risk of toxic protein aggreg ...

2025

Hsp110 Nucleotide Exchange Factors may amplify Hsp70-disaggregation by enhanced entropic pulling

Paolo De Los Rios, Bruno Claude Daniel Fauvet, Mathieu Rebeaud

Hsp70s use energy from ATP hydrolysis to unfold protein structures and solubilize stable aggregates and accumulate native species, even under adverse non-native conditions. To carry out its catalytic polypeptide-unfolding activity, Hsp70 needs to reversibl ...

Elsevier BV2025

Minimal Model for Carnot Efficiency at Maximum Power

Paolo De Los Rios, Shiling Liang

Carnot efficiency sets a fundamental upper bound on the heat engine efficiency, attainable in the quasistatic limit, albeit at the cost of completely sacrificing power output. Here, we present a minimal heat engine model that can attain Carnot efficiency w ...

2025

Phase boundaries promote chemical reactions through localized fluxes

Paolo De Los Rios, Alexandra Shelest, Hugo Camille Valentin Le Roy

One of the hypothesized functions of biomolecular condensates is to act as chemical reactors, where chemical reactions can be modulated, i.e., accelerated or slowed down, while substrate molecules enter and products exit from the condensate. Similarly, the ...

2025

Thermodynamic Bounds on Symmetry Breaking in Linear and Catalytic Biochemical Systems

Paolo De Los Rios, Shiling Liang

Living systems are maintained out of equilibrium by external driving forces. At stationarity, they exhibit emergent selection phenomena that break equilibrium symmetries and originate from the expansion of the accessible chemical space due to nonequilibriu ...

2024

Autorepression of yeast Hsp70 cochaperones by intramolecular interactions involving their J-domains

Paolo De Los Rios, Bruno Claude Daniel Fauvet, Adélaïde Alice Mohr, Satyam Tiwari, Mathieu Rebeaud, Pierre Goloubinoff

The 70 kDa heat shock protein (Hsp70) chaperones control protein homeostasis in all ATP-containing cellular compartments. J-domain proteins (JDPs) coevolved with Hsp70s to trigger ATP hydrolysis and catalytically upload various substrate polypeptides in ne ...

Elsevier Science Inc2024

J-domain proteins: From molecular mechanisms to diseases

Paolo De Los Rios, Mathieu Rebeaud

Here, we report on the latest findings related to JDP functions presented at a dedicated JDP workshop in Gdansk, Poland. The report does not include all (details) of what was shared and discussed at the meeting, because some of these original data have not ...

2024

Single-molecule evidence of Entropic Pulling by Hsp70 chaperones

Paolo De Los Rios, Chan Cao, Mathieu Rebeaud

Hsp70 chaperones are central components of the cellular network that ensures the structural quality of proteins. Despite crucial roles in processes such as protein disaggregation and protein translocation into organelles, their physical mechanism of action ...

Nature Research2024

An outmoded in vitro-inferred mechanism for chaperonin-accelerated protein refolding is confirmed in cells by cryo-electron tomography

Paolo De Los Rios, Mathieu Rebeaud

ELSEVIER SCIENCE INC2024

ABC transporters are billion-year-old Maxwell Demons

Paolo De Los Rios, Solange Marie Flatt, Stefano Zamuner, Daniel Maria Busiello

ATP-Binding Cassette (ABC) transporters are a broad family of biological machines, found in most prokaryotic and eukaryotic cells, performing the crucial import or export of substrates through both plasma and organellar membranes, and maintaining a steady ...

NATURE PORTFOLIO2023

Second Virtual International Symposium on Cellular and Organismal Stress Responses, September 8-9, 2022

Paolo De Los Rios, Wei Li, Pierre Goloubinoff

The Second International Symposium on Cellular and Organismal Stress Responses took place virtually on September 8-9, 2022. This meeting was supported by the Cell Stress Society International (CSSI) and organized by Patricija Van OostenHawle and Andrew Tru ...

SPRINGER2023

Data-driven large-scale genomic analysis reveals an intricate phylogenetic and functional landscape in J-domain proteins

Paolo De Los Rios, Duccio Malinverni, Alessandro Barducci, Stefano Zamuner, Mathieu Rebeaud

The 70-kD heat shock protein (Hsp70) chaperone system is a central hub of the proteostasis network that helps maintain protein homeostasis in all organisms. The recruitment of Hsp70 to perform different and specific cellular functions is regulated by the J ...

National Academy of Sciences2023

Individual and combined benefits of different nonequilibrium proofreading mechanisms

Paolo De Los Rios, Adélaïde Alice Mohr, Stefano Zamuner, Daniel Maria Busiello

Genome duplication, transcription, and translation are among many crucial cellular processes that need to be performed with high fidelity. However, those extremely low error rates cannot be explained with simple equilibrium thermodynamic considerations. Th ...

Amer Physical Soc2023

CERT1 mutations perturb human development by disrupting sphingolipid homeostasis

Paolo De Los Rios, Bruno Lemaitre, Evelyne Ruchti, Sylvia Ho, Anthony Vocat, Samuel Rommelaere, Greta Limoni, Stefano Zamuner, Giovanni D'Angelo, Laura Capolupo, Charlotte Julie Caroline Gehin, Huixin Guo

Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are ...

American Society for Clinical Investigation2023

Emergent thermophoretic behavior in chemical reaction systems

Paolo De Los Rios, Shiling Liang, Daniel Maria Busiello

Exposing a solution to a temperature gradient can lead to the accumulation of particles on either the cold or warm side. This phenomenon is known as thermophoresis, and its microscopic origin is still debated. Here, we show that thermophoresis can be obser ...

IOP Publishing Ltd2022

J-domain protein chaperone circuits in proteostasis and disease

Paolo De Los Rios, Duccio Malinverni, Ruobing Zhang

The J-domain proteins (JDP) form the largest protein family among cellular chaperones. In cooperation with the Hsp70 chaperone system, these co-chaperones orchestrate a plethora of distinct functions, including those that help maintain cellular proteostasi ...

ELSEVIER SCIENCE LONDON2022

A fluorescent multi-domain protein reveals the unfolding mechanism of Hsp70

Paolo De Los Rios, Bruno Claude Daniel Fauvet, Salvatore Assenza, Satyam Tiwari, Pierre Goloubinoff

Detailed understanding of the mechanism by which Hsp70 chaperones protect cells against protein aggregation is hampered by the lack of a comprehensive characterization of the aggregates, which are typically heterogeneous. Here we designed a reporter chaper ...

NATURE PORTFOLIO2022

Dissipation-driven selection of states in non-equilibrium chemical networks

Paolo De Los Rios, Francesco Piazza, Shiling Liang, Daniel Maria Busiello

Life has most likely originated as a consequence of processes taking place in non-equilibrium conditions (e.g. in the proximity of deep-sea thermal vents) selecting states of matter that would have been otherwise unfavorable at equilibrium. Here we present ...

2021

Ant behavioral maturation is mediated by a stochastic transition between two fundamental states

Paolo De Los Rios, Matthias Rüegg

The remarkable ecological success of social insects is often attributed to their advanced division of labor, which is closely associated with temporal polyethism in which workers transition between different tasks as they age. Young nurses are typically fo ...

CELL PRESS2021

Relief of ParB autoinhibition by parS DNA catalysis and recycling of ParB by CTP hydrolysis promote bacterial centromere assembly

Paolo De Los Rios, Stefano Zamuner

Three-component ParABS systems are widely distributed factors for plasmid partitioning and chromosome segregation in bacteria. ParB acts as adaptor protein between the 16-base pair centromeric parS DNA sequences and the DNA segregation proteins ParA and Sm ...

AMER ASSOC ADVANCEMENT SCIENCE2021