Mitochondrial calcium uniporter regulatory subunit beta (MCUb)

Mitochondrial calcium uniporter regulatory subunit beta (MCUb) is a transmembrane protein located in the inner mitochondrial membrane and is a paralog of the pore-forming mitochondrial calcium uniporter (MCU)[1][2][4]. MCUb has two coiled-coil domains and two transmembrane regions, and it incorporates into the MCU complex through hetero-oligomerization with MCU[1][2]. Distinguished by a critical Glu-to-Val substitution in its pore region, MCUb functions as an endogenous dominant-negative regulator—its presence within channel oligomers sharply reduces or blocks Ca²⁺ conductance by impairing the pore structure[1][2][3]. Overexpression of MCUb suppresses mitochondrial calcium uptake, while knockdown increases uptake, underlining its central inhibitory role[1][2]. MCUb thereby fine-tunes aerobic metabolism, controls apoptosis, and prevents calcium overload, with key regulatory effects in tissues like heart and skeletal muscle[1][3][4]. It also modulates immune cell metabolism and tissue regeneration by controlling calcium influx during stress and inflammatory responses[3][4]. No drugs are currently known to specifically target MCUb directly; it is mainly recognized as a potential therapeutic target in diseases involving mitochondrial dysfunction, calcium overload, or metabolic imbalance[2][4].

Other names

MCUbCCDC109BCoiled-coil domain-containing protein 109BFLJ20647Mitochondrial calcium uniporter dominant negative subunit betaMitochondrial calcium uniporter dominant negative beta subunit

Inhibition of mitochondrial calcium influx by forming dominant-negative channel complexes with MCU