According to our results, decreased level of OXPHOS subunit proteins (complex III, IV, and V), mitochondrial content (determined by enzymatic activity), and regulatory proteins of mitochondrial dynamics (Drp1 and Mfn2), were corrected by the voluntary exercise intervention, thereby suggesting that physical exercise is an effective therapeutic strategy to reduce mitochondrial abnormality associated with cancer cachexia. Here, MFN2 is linked to cancer.