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Title: Autophagy exacerbates muscle wasting in cancer cachexia and impairs mitochondrial function
Author: Penna, Fabio
Ballaro, Riccardo
Martínez Cristóbal, Paula
Sala Cano, David
Sebastián Muñoz, David
Busquets Rius, Sílvia
Muscaritoli, Maurizio
Argilés Huguet, Josep Ma.
Costelli, Paola
Zorzano Olarte, Antonio
Keywords: Autofàgia
Issue Date: 12-Jul-2019
Publisher: Elsevier Ltd
Abstract: Cancer cachexia is a multifactorial syndrome characterized by anorexia, weight loss and muscle wasting that impairs patients' quality of life and survival. Aim of this work was to evaluate the impact of either autophagy inhibition (knocking down beclin-1) or promotion (overexpressing TP53INP2/DOR) on cancer-induced muscle wasting. In C26 tumor-bearing mice, stress-induced autophagy inhibition was unable to rescue the loss of muscle mass and worsened muscle morphology. Treating C26-bearing mice with formoterol, a selective β2-agonist, muscle sparing was paralleled by reduced static autophagy markers, although the flux was maintained. Conversely, the stimulation of muscle autophagy exacerbated muscle atrophy in tumor-bearing mice. TP53INP2 further promoted atrogene expression and suppressed mitochondrial dynamics-related genes. Excessive autophagy might impair mitochondrial function through mitophagy. Consistently, tumor-induced mitochondrial dysfunction was detected by reduced ex vivo muscle fiber respiration. Overall, the results evoke a central role for muscle autophagy in cancer-induced muscle wasting.
Note: Versió postprint del document publicat a:
It is part of: Journal of Molecular Biology, 2019, vol. 431, num. 15, p. 2674-2686
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ISSN: 0022-2836
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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