2026-08-05T11:42:03Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/138882024-10-31T11:47:47Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Herrero-Galan, Elas
author
Martinez-Martin, Ines
author
Sanchez-Gonzalez, Cristina
author
Vicente, Natalia
author
Bonzon-Kulichenko, Elena
author
Calvo, Enrique
author
Suay-Corredera, Carmen
author
Pricolo, Maria Rosaria
author
Fernández-Trasancos, Ángel
author
Velázquez-Carreras, Diana
author
Badia-Careaga, Claudio
author
Abdellatif, Mahmoud
author
Sedej, Simon
author
Rainer, Peter P.
author
Giganti, David
author
Pérez-Jiménez, Raúl
author
Vazquez, Jesus
author
Alegre-Cebollada, Jorge
funder
Ministerio de Ciencia e Innovación (España)
funder
Comunidad de Madrid (España)
funder
Instituto de Salud Carlos III
funder
Fundación La Caixa
funder
FWF Austrian Science Fund
funder
Fundación ProCNIC
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
2022-03-29T12:04:07Z
2022-03-29T12:04:07Z
2022-03-28
Redox Biol. 2022; 102306
10.1016/j.redox.2022.102306
2213-2317
2213-2317
Redox Biology
http://hdl.handle.net/20.500.12105/13888
Titin, as the main protein responsible for the passive stiffness of the sarcomere, plays a key role in diastolic function and is a determinant factor in the etiology of heart disease. Titin stiffness depends on unfolding and folding transitions of immunoglobulin-like (Ig) domains of the I-band, and recent studies have shown that oxidative modifications of cryptic cysteines belonging to these Ig domains modulate their mechanical properties in vitro. However, the relevance of this mode of titin mechanical modulation in vivo remains largely unknown. Here, we describe the high evolutionary conservation of titin mechanical cysteines and show that they are remarkably oxidized in murine cardiac tissue. Mass spectrometry analyses indicate a similar landscape of basal oxidation in murine and human myocardium. Monte Carlo simulations illustrate how disulfides and S-thiolations on these cysteines increase the dynamics of the protein at physiological forces, while enabling load- and isoform-dependent regulation of titin stiffness. Our results demonstrate the role of conserved cysteines in the modulation of titin mechanical properties in vivo and point to potential redox-based pathomechanisms in heart disease.
eng
Basal oxidation of conserved cysteines modulates cardiac titin stiffness and dynamics
journal article
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