Miniatura

Fitxers

876127.pdf (4.58 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2024-12-01

Llicència de publicació

cc-by (c) Fornelli, C. et al., 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/220113

BNIP3 Downregulation Ameliorates Muscle Atrophy in Cancer Cachexia

Títol de la revista

Autors

ISSN de la revista

Títol del volum

Resum

Background and aims: Cancer cachexia is a complex syndrome affecting most cancer patients and is directly responsible for about 20% of cancer-related deaths. Previous studies showed muscle proteolysis hyper-activation and mitophagy induction in tumor-bearing animals. While basal mitophagy is required for maintaining muscle mass and quality, excessive mitophagy promotes uncontrolled protein degradation, muscle loss and impaired function. BNIP3, a key mitophagy-related protein, is significantly increased in the muscles of both mice and human cancer hosts. This study aimed to define the potential of mitigating mitophagy via BNIP3 downregulation in preserving mitochondrial integrity, counteracting skeletal muscle loss in experimental cancer cachexia. Methods: Two in vivo gene delivery methods were performed to knock down muscle BNIP3: electroporation of a BNIP3-specific shRNA expression vector or adenovirus injection. Results: The electroporation effectively reduced muscle BNIP3 in healthy mice but was ineffective in C26 tumor-bearing mice. In contrast, adenovirus-mediated BNIP3 knockdown successfully decreased BNIP3 levels also in tumor hosts. Although BNIP3 knockdown did not impact overall on body or muscle mass, it improved muscle fiber size in C26-bearing miceh2, suggesting partial prevention of muscle atrophy. Mitochondrial respiratory chain complexes (OxPhos) and TOM20 protein levels were consistently rescued, indicating improvements in mitochondrial mass, while H2O2 levels were unchanged among the groups, suggesting that BNIP3 downregulation does not impair the endogenous control of oxidative balance. Conclusions: These findings suggest that a fine balance between mitochondrial disposal and biogenesis is fundamental for preserving muscle homeostasis and highlight a potential role for BNIP3 modulation against cancer-induced muscle wasting. Keywords: BNIP3; cancer cachexia; mitochondria; mitophagy; muscle wasting.

Descripció

Matèries

Càncer, Atròfia muscular, Caquèxia, Autofàgia

Matèries (anglès)

Cancer, Muscular atrophy, Cachexia, Autophagy

Citació

Col·leccions

Articles publicats en revistes (Bioquímica i Fisiologia)
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

FORNELLI, Claudia, BELTRÀ, Marc, ZORZANO OLARTE, Antonio, COSTELLI, Paola, SEBASTIÁN MUÑOZ, David, PENNA, Fabio. BNIP3 Downregulation Ameliorates Muscle Atrophy in Cancer Cachexia. _Cancers_. 2024. Vol. 16, núm. 24. [consulta: 25 de novembre de 2025]. ISSN: 2072-6694. [Disponible a: https://hdl.handle.net/2445/220113]

Exportar metadades

JSON - METS

Compartir registre