The Relationship of Cholesterol Responses to Mitochondrial Dysfunction and Lung Inflammation in Chronic Obstructive Pulmonary Disease

Abstract

Hyperlipidemia is frequently reported in chronic obstructive pulmonary disease (COPD) patients and is linked to the progression of the disease and its comorbidities. Hypercholesterolemia leads to cholesterol accumulation in many cell types, especially immune cells, and some recent studies suggest that cholesterol impacts lung epithelial cells’ inflammatory responses and mitochondrial responses. Several studies also indicate that targeting cholesterol responses with either statins or liver X receptor (LXR) agonists may be plausible means of improving pulmonary outcomes. Equally, cholesterol metabolism and signaling are linked to mitochondrial dysfunction and inflammation attributed to COPD progression. Here, we review the current literature focusing on the impact of cigarette smoke on cholesterol levels, cholesterol efflux, and the influence of cholesterol on immune and mitochondrial responses within the lungs.

Loss of lysosomal acid lipase results in mitochondrial dysfunction and fiber switch in skeletal muscles of mice

“…Loss of LAL is associated with ectopic accumulation of lipids, especially CE [ 12 , 16 , 58 , 72 , 73 ], also in SM [ 74 ]. Cholesterol accumulation may contribute to mitochondrial dysfunction, including reduced respiration and decreased ATP production [ 75 , 76 ] in Lal−/− SM. The previously described rapid development of fatigue and the reduction in ATP turnover of the SM [ 77 ] is consistent with the Lal−/− SM mitochondrial dysfunction and the reduction in ATP concentration.…”