Figure 2.

The co-existence of two functionally different mitochondria within the brown adipocyte. A scheme of two types of mitochondria identified in the brown adipocyte: cytosolic mitochondria (CM) and peridroplet mitochondria (PDM) (74–78). PDM are anchored to the lipid droplets and segregated from the pool of CM. CM preferentially oxidize FA and are more thermogenic compared to PDM. FAO-induced increases in acetyl-CoA/CoA and NADH/NAD⁺ ratios would inhibit PDH in the matrix, resulting in a decrease in pyruvate-derived citrate production and subsequent malonyl-CoA accumulation in close vicinity of CM. FA-derived citrate would be rapidly oxidized through the TCA cycle to support UCP1-mediated thermogenesis. On the contrary, PDM have a higher capacity for pyruvate oxidation and ATP synthesis compared to CM. Given that coupled respiration is dependent on ADP availability, excess citrate would escape from the mitochondria and be converted to malonyl-CoA by ACC1 and ACC2, thus contributing to de novo lipogenesis and simultaneously preventing CPT1β-mediated FA entry into PDM. The co-existence of two functionally different mitochondria within the brown adipocyte may in part explain the concurrence of glycolysis, FA synthesis, and FA oxidation in brown adipocytes. FA, fatty acids; ETC, electron transport chain; CPT, carnitine palmitoyltransferase; UCP1, uncoupled protein 1; TCA, the tricarboxylic acid cycle; OAA, oxaloacetate; MPC, mitochondrial pyruvate carrier; PDH, pyruvate dehydrogenase; PC, pyruvate carboxylase; ACLY, ATP-citrate lyase; ACC, acetyl-CoA carboxylases; FAS, fatty acid synthase; TAG, triacylglycerol.