Bone metastases induce metabolic changes and mitophagy in mice

Jenna Wilcox-Hagerty, Haifang Xu, Brian A. Hain, Amy C. Arnold, David L. Waning

Research output: Contribution to journalArticlepeer-review

Abstract

New Findings: What is the central question of this study? Cachexia causes severe changes in skeletal muscle metabolism and function and is a key predictor of negative outcomes in cancer patients: what are the changes in whole animal energy metabolism and mitochondria in skeletal muscle? What is the main finding and its importance? There is decreased whole animal energy expenditure in mice with cachexia. They displayed highly dysmorphic mitochondria and mitophagy in skeletal muscle. Abstract: Cachexia causes changes in skeletal muscle metabolism. Mice with MDA-MB-231 breast cancer bone metastases and cachexia have decreased whole animal energy metabolism and increased skeletal muscle mitophagy. We examined whole animal energy metabolism by indirect calorimetry in mice with MDA-MB-231 breast cancer bone metastases, and showed decreased energy expenditure. We also examined skeletal muscle mitochondria and found that mitochondria in mice with MDA-MB-231 bone metastases are highly dysmorphic and have altered protein markers of mitochondrial biogenesis and dynamics. In addition, LC3B protein was increased in mitochondria of skeletal muscle from cachectic mice, and colocalized with the mitochondrial protein Tom20. Our data demonstrate the importance of mitophagy in cachexia. Understanding these changes will help contribute to defining treatments for cancer cachexia.

Original languageEnglish (US)
Pages (from-to)506-518
Number of pages13
JournalExperimental Physiology
Volume106
Issue number2
DOIs
StatePublished - Feb 1 2021

All Science Journal Classification (ASJC) codes

  • Physiology
  • Nutrition and Dietetics
  • Physiology (medical)

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