Mitochondrial and sarcoplasmic reticulum abnormalities in cancer cachexia: Altered energetic efficiency?

Background: Cachexia is awasting condition thatmanifests in several types of cancer, and themain characteristic is the profound loss of muscle mass. Methods: The Yoshida AH-130 tumormodel has been used and the samples have been analyzed using transmission electronic microscopy, real-time PCR andWestern blot techniques. Results: Using in vivo cancer cachectic model in rats, here we show that skeletal muscle loss is accompanied by fibermorphologic alterations such asmitochondrial disruption, dilatation of sarcoplasmic reticulum and apoptotic nuclei. Analyzing the expression of some factors related to proteolytic and thermogenic processes, we observed in tumor-bearing animals an increased expression of genes involved in proteolysis such as ubiquitin ligasesMuscle Ring Finger 1 (MuRF-1) and Muscle Atrophy F-box protein (MAFBx). Moreover, an overexpression of both sarco/endoplasmic Ca2+-ATPase (SERCA1) and adenine nucleotide translocator (ANT1), both factors related to cellular energetic efficiency,was observed. Tumor burden also leads to amarked decreased inmuscle ATP content. Conclusions: In addition to muscle proteolysis, other ATP-related pathways may have a key role in muscle wasting, both directly by increasing energetic inefficiency, and indirectly, by affecting the sarcoplasmic reticulum–mitochondrial assembly that is essential for muscle function and homeostasis. General significance: The present study reports profound morphological changes in cancer cachectic muscle, which are visualized mainly in alterations in sarcoplasmic reticulum and mitochondria. These alterations are linked to pathways that can account for energy inefficiency associated with cancer cachexia.