MCU genetically altered mice suggest how mitochondrial Ca < sup > 2+ < /sup > regulates metabolism

Trends Endocrinol Metab. 2024 Apr 29:S1043-2760(24)00088-2. doi: 10.1016/j.tem.2024.04.005. Online ahead of print.ABSTRACTSkeletal muscle has a major impact on total body metabolism and obesity, and is characterized by dynamic regulation of substrate utilization. While it is accepted that acute increases in mitochondrial matrix Ca2+ increase carbohydrate usage to augment ATP production, recent studies in mice with deleted genes for components of the mitochondrial Ca2+ uniporter (MCU) complex have suggested a more complicated regulatory scenario. Indeed, mice with a deleted Mcu gene in muscle, which lack acute mitochondrial Ca2+ uptake, have greater fatty acid oxidation (FAO) and less adiposity. By contrast, mice deleted for the inhibitory Mcub gene in skeletal muscle, which have greater acute mitochondrial Ca2+ uptake, antithetically display reduced FAO and progressive obesity. In this review we discuss the emerging concept that dynamic fluxing of mitochondrial matrix Ca2+ regulates metabolism.PMID:38688781 | DOI:10.1016/j.tem.2024.04.005
Source: Trends in Endocrinology and Metabolism: TEM - Category: Endocrinology Authors: Source Type: research