Figure 3. Consequences of CMA malfunctioning in cellular energetics.

Blockage of CMA activity in liver and fibroblasts in culture results in abnormally increased glycolytic flux and lipogenesis. However, the energetic balance is negative and the ATP low, due to the inability to mobilize the stored lipid through lipolysis. Abnormal upregulation of CMA has also shown to alter cellular energetics in two different pathological conditions. In these cases, high rates of degradation of a key glycolytic enzyme by CMA reduce glycolytic flux and cellular energetics. Although there is no information on lipid metabolism under these conditions it is anticipated that reduced lipogenesis may also contribute to inefficient lipid handling in this disease context.