Role of mitochondrial dysfunction in muscle wasting in cancer cachexia: a narrative review.

backgroundCancer cachexia is a complex syndrome characterized by significant muscle loss, weight loss, and impaired physical function. One of the core causes of excessive muscle wasting in cancer cachexia patients is mitochondrial dysfunction, which disrupts the energy production and metabolism necessary for muscle function and repair. This review summarizes and synthesizes current evidence on how mitochondrial dysfunction and its associated molecular mechanisms contribute to muscle atrophy in cancer cachexia. MAIN BODY: Mitochondria in muscle cells contribute to maintaining muscle contraction and metabolic activities. Mitochondrial dysfunction, including alterations in mitochondrial biogenesis, mitophagy, and mitochondrial dynamics (fission and fusion), occurs in cancer cachexia. These disturbances result in an insufficient energy supply in muscle cells, leading to excessive muscle wasting. Activation of inflammatory pathways, increased production of reactive oxygen species (ROS), and impairment of mitochondrial protein synthesis pathways are key factors contributing to this dysfunction. Successful restoration of mitochondrial function offers hope for slowing muscle wasting induced by cancer cachexia. We explore various strategies that help restore mitochondrial function to prevent or alleviate muscle wasting. For example, the overexpression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), AMP-activated protein kinase (AMPK), and silent information regulator 1 (SIRT1), as well as regular exercise, can maintain mitochondrial health and help reduce muscle wasting. In addressing these complex mechanisms, we also discuss the potential of targeting mitochondrial dysfunction as a therapeutic strategy for muscle wasting in cancer cachexia through agents such as small molecule inhibitors of mitochondrial dynamics, antioxidants targeting mitochondrial ROS, natural products such as curcumin, and nutritional supplements such as leucine and creatine.

conclusionsRestoration of mitochondrial function is a promising strategy to combat excessive muscle wasting induced by cancer cachexia. Further research on the precise regulation of mitochondrial dynamics and clinical trials of targeted therapies are crucial for the development of effective methods to treat cancer-associated muscle wasting.