Fig. 8: Mechanism by which brown adipocytes avoid cell death during thermogenesis.

Adrenergic stimulation of brown adipocytes leads to intracellular increase in Ca²⁺ which can induce mitochondrial Ca²⁺ overload and permeability transition. While in other cell types, such scenario will progress to apoptosis, in BA, adrenergic stimulation leads to activation of Ca²⁺ extrusion through NCLX, thereby preventing permeability transition and cell death. Inhibition of permeability transition using the Cyclophilin D inhibitor, NIM811, can prevent cell death and restore function even in the absence of NCLX, and while Ca²⁺ overload persists. _iCa²⁺, intracellular \({\mathrm{Ca}}^{{\mathrm{2 + }}}\); _m\({\mathrm{Ca}}^{2 + }\), mitochondrial \({\mathrm{Ca}}^{2 + }\).