Tissue-specific dysregulation of mitochondrial respiratory capacity and coupling control in colon-26 tumor-induced cachexia

• DOI: 10.1152/ajpregu.00028.2019
• Publication Date: 2019-04-24T18:46:21Z
• Authors: Jessica L. Halle; Gabriel S. Pena; Hector G. Paez; Adrianna J. Castro; Harry B. Rossiter; Nishant P. Visava...; Michael A. Whiteh...; Andy V. Khamoui
• Keywords: Male; 0303 health sciences; Cachexia; Oxidative Coupling; Cardiolipins; Adenine Nucleotide Translocator 2; Neoplasms, Experimental; Mitochondria, Muscle; 3. Good health; Mice; Random Allocation; 03 medical and health sciences; Oxygen Consumption; Liver; Colonic Neoplasms; Weight Loss; Animals; Muscle, Skeletal; Reactive Oxygen Species

In addition to skeletal muscle dysfunction, cancer cachexia is a systemic disease involving remodeling of nonmuscle organs such as adipose and liver. Impairment mitochondrial function associated with multiple chronic diseases. The tissue-specific control in not well defined. This study determined respiratory capacity coupling muscle, white tissue (WAT), liver colon-26 (C26) tumor-induced cachexia. Tissues were collected from PBS-injected weight-stable mice, C26 mice moderate (10% weight loss) severe (20% loss). ratio [(RCR) an index oxidative phosphorylation (OXPHOS) efficiency] was low WAT during the induction because high nonphosphorylating LEAK respiration. Liver RCR moderately cachexic reduced OXPHOS. further cachexia, where Ant2 but Ucp2 expression increased. inversely correlated ( r = −0.547, P < 0.01). cardiolipin increased suggesting this early event may also contribute uncoupling. Impaired respiration occurred predominantly at complex I. These findings suggest that subject whereby arise altered energy balance, followed by impaired We highlight under-recognized role tissues be therapeutic targets.