Mitochondrial Dysfunction in Cancer Cachexia: Impact on Muscle Health and Regeneration

Abstract

Cancer cachexia is a frequently neglected debilitating syndrome that, beyond representing a primary cause of death and cancer therapy failure, negatively impacts on patients’ quality of life. Given the complexity of its multisystemic pathogenesis, affecting several organs beyond the skeletal muscle, defining an effective therapeutic approach has failed so far. Revamped attention of the scientific community working on cancer cachexia has focused on mitochondrial alterations occurring in the skeletal muscle as potential triggers of the complex metabolic derangements, eventually leading to hypercatabolism and tissue wasting. Mitochondrial dysfunction may be simplistically viewed as a cause of energy failure, thus inducing protein catabolism as a compensatory mechanism; however, other peculiar cachexia features may depend on mitochondria. On the one side, chemotherapy also impacts on muscle mitochondrial function while, on the other side, muscle-impaired regeneration may result from insufficient energy production from damaged mitochondria. Boosting mitochondrial function could thus improve the energetic status and chemotherapy tolerance, and relieve the myogenic process in cancer cachexia. In the present work, a focused review of the available literature on mitochondrial dysfunction in cancer cachexia is presented along with preliminary data dissecting the potential role of stimulating mitochondrial biogenesis via PGC-1α overexpression in distinct aspects of cancer-induced muscle wasting.

Sex Differences in Cardiac Pathology of SARS-CoV2 Infected and Trypanosoma cruzi Co-infected Mice

“…The reduced levels of SOD in the hearts in coinfected female mice also suggest increased oxidative stress and mitochondrial dysfunction in these mice. Increased mitochondrial dysfunction is associated with cachexia and atrophy ( 61 , 62 ). On the other hand, in coinfected males, the cardiac accumulation of HMW-ApN and AMPK activation may increase glycolysis and also adipogenesis, which may cause lipotoxicity leading to cardiac steatosis, hypertrophy and early dilated cardiomyopathy in post-COVID mice.…”

NAD+repletion with niacin counteracts cancer cachexia

“…Muscle mitochondrial dysfunction has gained importance in recent years as a crucial feature of CC 19 . In the current experiments, the skeletal muscle of C26-F mice presented with reduced protein levels of the main activator of mitochondrial biogenesis PGC-1α (Fig 4a, b), a decline in mitochondrial DNA (mtDNA) amount (Fig.…”

“…Muscle mitochondrial dysfunction has gained importance in recent years as a crucial feature of CC 19 .…”

The Mitochondria-Targeting Agent MitoQ Improves Muscle Atrophy, Weakness and Oxidative Metabolism in C26 Tumor-Bearing Mice

“…Lastly, in our study we failed to report on the antioxidant properties of MitoQ in the skeletal muscle of tumor hosts. Keeping in mind our previous observations demonstrating that chemotherapy, similar to cancer, also promotes mitochondrial abnormalities and higher levels of reactive oxygen species, which in turn contribute to the development of skeletal muscle dysfunction in cachexia ( Barreto et al, 2016a ; Barreto et al, 2016b ; Brown et al, 2017 ; Ballaro et al, 2021 ; Beltra et al, 2021 ), future studies will need to validate the anti-cachectic properties of MitoQ also in combination with routinely administered anticancer agents.…”