Could Cytoplasmic Lipid Droplets be Linked to Inefficient Oxidative Phosphorylation in Cancer?

Triglyceride-rich cytoplasmic lipid droplets are present in many malignant cancers. It remains controversial as to whether the lipid droplets serve as reservoirs of respiratory fuel or are sequestered in droplets because they cannot be efficiently oxidized for energy. Cytoplasmic lipid droplets can arise from either hypoxia or from abnormalities in mitochondria structure and function. A hypothesis is presented suggesting that the lipid droplet accumulation is linked to inefficient oxidative phosphorylation.

Evidence is reviewed showing that hypoxia-induced inhibition of oxidative phosphorylation can elicit the formation of cytoplasmic lipid droplets. Abnormalities in mitochondrial structure and function have been documented in malignant cancers where lipid droplets are also present.

The mitochondrial abnormalities seen in cancer cells would compromise the efficiency of oxidative phosphorylation and thus contribute to the accumulation of lipid droplets in the cytoplasm. The presence of cytoplasmic lipid droplets and the aerobic fermentation commonly seen in most malignant cancers can serve together as biomarkers for oxidative phosphorylation inefficiency.