title: Altered mitochondrial quality control signaling in muscle of old gastric cancer patients with cachexia.
abstract: Mitochondrial dysfunction is involved in the loss of muscle featuring both aging and cancer cachexia (CC). Whether mitochondrial quality control (MQC) is altered in skeletal myocytes of old patients with CC is unclear. The present investigation therefore sought to preliminarily characterize MQC pathways in muscle of old gastric cancer patients with cachexia. The study followed a case-control cross-sectional design. Intraoperative biopsies of the rectus abdominis muscle were obtained from 18 patients with gastric adenocarcinoma (nine with CC and nine non-cachectic) and nine controls, and assayed for the expression of a set of MQC mediators. The mitofusin 2 expression was reduced in cancer patients compared with controls, independent of CC. Fission protein 1 was instead up-regulated in CC patients relative to the other groups. The mitophagy regulators PTEN-induced putative kinase 1 and Parkin were both down-regulated in cancer patients compared with controls. The ratio between the protein content of the lipidated and non-lipidated forms of microtubule-associated protein 1 light chain 3B was lower in CC patients relative to controls and non-cachectic cancer patients. Finally, the expression of autophagy-associated protein 7, lysosome-associated membrane protein 2, peroxisome proliferator-activated receptor-γ coactivator-1α, and mitochondrial transcription factor A was unvarying among groups. Collectively, our findings indicate that, in old patients with gastric cancer, cachexia is associated with derangements of the muscular MQC axis at several checkpoints: mitochondrial dynamics, mitochondrial tagging for disposal, and mitophagy signaling. Further investigations are needed to corroborate these preliminary findings and determine whether MQC pathways may become target for future interventions.
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome 00168, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Marzetti
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome 00168, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Lorenzi
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome 00168, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Landi
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome 00168, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Picca
authors.affiliation: Department of Surgery, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome 00168, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Rosa
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome 00168, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Tanganelli
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome 00168, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Galli
authors.affiliation: Department of Surgery, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome 00168, Italy.
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Doglietto
authors.affiliation: Department of Surgery, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome 00168, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pacelli
authors.affiliation: Gérontopôle, Centre Hospitalier Universitaire de Toulouse, Toulouse 31000, France; Université de Toulouse III Paul Sabatier, Toulouse 31000, France.
authors.forename: Matteo
authors.initials: M
authors.lastname: Cesari
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome 00168, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bernabei
authors.affiliation: Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome 00168, Italy. Electronic address: riccardo.calvani@gmail.com.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Calvani
authors.affiliation: Department of Surgery, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital "Agostino Gemelli", Rome 00168, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bossola
mesh_terms: D000230:Adenocarcinoma / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology; D002100:Cachexia / Q000209:etiology / Q000503:physiopathology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism*; D063269:Mitochondrial Turnover; D063306:Mitophagy; D018482:Muscle, Skeletal / Q000473:pathology*; D018384:Oxidative Stress; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000503:physiopathology*
chemical_list: D047492:Peroxisome Proliferator-Activated Receptors
keywords: Bioenergetics; Cachexia; Mitochondrial biogenesis; Mitochondrial dynamics; Mitophagy; Muscle wasting