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Delfinis 2022 JCI Insight

From Bioblast
Publications in the MiPMap
Delfinis LJ, Bellissimo CA, Gandhi S, DiBenedetto SN, Garibotti MC, Thuhan AK, Tsitkanou S, Rosa-Caldwell ME, Rahman FA, Cheng AJ, Wiggs MP, Schlattner U, Quadrilatero J, Greene NP, Perry CG (2022) Muscle weakness precedes atrophy during cancer cachexia and is linked to muscle-specific mitochondrial stress. https://doi.org/10.1172/jci.insight.155147

ยป JCI Insight 7:e155147. PMID: 36346680 Open Access

Delfinis Luca J, Bellissimo Catherine A, Gandhi Shivam, DiBenedetto Sara N, Garibotti Madison C, Thuhan Arshkeep K, Tsitkanou Stavroula, Rosa-Caldwell Megan E, Rahman Fasih A, Cheng Arthur J, Wiggs Michael P, Schlattner Uwe, Quadrilatero Joe, Greene Nicholas P, Perry Christopher G (2022) JCI Insight

Abstract: Muscle weakness and wasting are defining features of cancer-induced cachexia. Mitochondrial stress occurs before atrophy in certain muscles, but the possibility of heterogeneous responses between muscles and across time remains unclear. Using mice inoculated with Colon-26 (C26) cancer, we demonstrate that specific force production was reduced in quadriceps and diaphragm at 2 weeks in the absence of atrophy. At this time, pyruvate-supported mitochondrial respiration was lower in quadriceps while mitochondrial H2O2 emission was elevated in diaphragm. By 4 weeks, atrophy occurred in both muscles, but specific force production increased to control levels in quadriceps such that reductions in absolute force were due entirely to atrophy. Specific force production remained reduced in diaphragm. Mitochondrial respiration increased and H2O2 emission was unchanged in both muscles vs control while mitochondrial creatine sensitivity was reduced in quadriceps. These findings indicate muscle weakness precedes atrophy and is linked to heterogeneous mitochondrial alterations that could involve adaptive responses to metabolic stress. Eventual muscle-specific restorations in force and bioenergetics highlight how the effects of cancer on one muscle do not predict the response in another muscle. Exploring heterogeneous responses of muscle to cancer may reveal new mechanisms underlying distinct sensitivities, or resistance, to cancer cachexia. โ€ข Keywords: Colorectal cancer, Metabolism, Mitochondria, Oncology, Skeletal muscle โ€ข Bioblast editor: Plangger M โ€ข O2k-Network Lab: FR Grenoble Schlattner U, CA Waterloo Quadrilatero J, CA Toronto Perry CG


Labels: MiParea: Respiration  Pathology: Cancer 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Regulation: PCr;Cr  Coupling state: LEAK, OXPHOS  Pathway:HRR: Oxygraph-2k 

2022-11