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Tag: MCJ (Page 1 of 2)

Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis

Beatriz Cicuéndez, Alfonso Mora, Juan Antonio López, Andrea Curtabbi, Javier Pérez-García, Begoña Porteiro, Daniel Jimenez-Blasco, Pedro Latorre-Muro, Paula Vo, Madison Jerome, Beatriz Gómez-Santos, Rafael Romero-Becerra, Magdalena Leiva, Elena Rodríguez, Marta León, Luis Leiva-Vega, Noemi Gómez-Lado, Jorge L. Torres, Lourdes Hernández-Cosido, Pablo Aguiar, Miguel Marcos, Martin Jastroch, Andreas Daiber, Patricia Aspichueta, Juan Pedro Bolaños, Jessica B. Spinelli, Pere Puigserver, José Antonio Enriquez, Jesús Vázquez, Cintia Folgueira & Guadalupe Sabio.

Obesity poses a global health challenge, demanding a deeper understanding of adipose tissue (AT) and its mitochondria. This study describes the role of the mitochondrial protein Methylation-controlled J protein (MCJ/DnaJC15) in orchestrating brown adipose tissue (BAT) thermogenesis.

Mitochondia from brown fat (Image: Beatriz Cicuéndez).

Here we show how MCJ expression decreases during obesity, as evident in human and mouse adipose tissue samples. MCJKO mice, even without UCP1, a fundamental thermogenic protein, exhibit elevated BAT thermogenesis. Electron microscopy unveils changes in mitochondrial morphology resembling BAT activation. Proteomic analysis confirms these findings and suggests involvement of the eIF2α mediated stress response. The pivotal role of eIF2α is scrutinized by in vivo CRISPR deletion of eIF2α in MCJKO mice, abrogating thermogenesis.

These findings uncover the importance of MCJ as a regulator of BAT thermogenesis, presenting it as a promising target for obesity therapy.

The IBSA Foundation awards Cintia Folgueira

The 11th edition of the IBSA Foundation fellowship program had a record number of projects received. A total of 248 applicants from over 50 countries.

Cintia Folgueira was awarded in Endocrinology with 32,000 € for her project Exploring new insights into brown adipose tissue mitochondria for protection against endocrine disorders. She will investigate valuable insights into prospective therapeutic targets for addressing obesity and related metabolic disorders, particularly by underscoring that the absence of mitochondrial proteins correlates with improvements in obesity, adiposity, and glucose tolerance.

The winner for the area “Endocrinology”, Cintia Folgueira Cobos.

MCJ: A mitochondrial target for cardiac intervention in pulmonary hypertension

Ayelén M. Santamans, Beatriz Cicuéndez, Alfonso Mora , María Villalba-Orero, Sanela Rajlic, María Crespo, Paula Vo, Madison Jerome, Álvaro Macías, Juan Antonio López, Magdalena Leiva, Susana F. Rocha, Marta León, Elena Rodríguez, Luis Leiva, Aránzazu Pintor Chocano, Inés García Lunar, Ana García-Álvarez, Pablo Hernansanz-Agustín, Víctor I. Peinado, Joan Albert Barberá, Borja Ibañez, Jesús Vázquez, Jessica B. Spinelli, Andreas Daiber, Eduardo Oliver & Guadalupe Sabio.

Pulmonary hypertension (PH) can affect both pulmonary arterial tree and cardiac function, often leading to right heart failure and death. Despite the urgency, the lack of understanding has limited the development of effective cardiac therapeutic strategies.

MCJ stainimg in lungs of patients with chronic obstructive pulmonary disease.

Our research reveals that MCJ modulates mitochondrial response to chronic hypoxia. MCJ levels elevate under hypoxic conditions, as in lungs of patients affected by COPD, mice exposed to hypoxia, and myocardium from pigs subjected to right ventricular (RV) overload. The absence of MCJ preserves RV function, safeguarding against both cardiac and lung remodeling induced by chronic hypoxia. Cardiac-specific silencing is enough to protect against cardiac dysfunction despite the adverse pulmonary remodeling. Mechanistically, the absence of MCJ triggers a protective preconditioning state mediated by the ROS/mTOR/HIF-1α axis. As a result, it preserves RV systolic function following hypoxia exposure.

These discoveries provide a potential avenue to alleviate chronic hypoxia-induced PH, highlighting MCJ as a promising target against this condition

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