Altered mitochondrial quality control in muscle of old cachectic patients with gastric cancer

Mitochondrial dysfunction has been involved in muscle wasting associated with cancer cachexia (CC). Whether mitochondrial quality control (MQC) is altered in skeletal myocytes during CC is still unclear. The present investigation sought to preliminarily characterize MQC pathways in muscle of 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 old 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. Mitofusin 2 (Mfn2) expression was reduced in cancer patients compared with controls, independent of CC, while fission protein 1 (Fis1) was up-regulated in CC patients relative to the other groups. As a result, the “fusion index” (Mfn2/Fis1 ratio) was lower in patients with CC. The mitophagy regulators PTEN-induced putative kinase 1 and Parkin were 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. In gastric cancer patients, 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 they may be targeted for interventions.