MCU-independent Ca²⁺ uptake mediates mitochondrial Ca²⁺ overload and necrotic cell death in a mouse model of Duchenne muscular dystrophy.

ABSTRACT: Mitochondrial Ca²⁺ overload can mediate mitochondria-dependent cell death, a major contributor to several human diseases. Indeed, Duchenne muscular dystrophy (MD) is driven by dysfunctional Ca²⁺ influx across the sarcolemma that causes mitochondrial Ca²⁺ overload, organelle rupture, and muscle necrosis. The mitochondrial Ca²⁺ uniporter (MCU) complex is the primary characterized mechanism for acute mitochondrial Ca²⁺ uptake. One strategy for preventing mitochondrial Ca²⁺ overload is deletion of the Mcu gene, the pore forming subunit of the MCU-complex. Conversely, enhanced MCU-complex Ca²⁺ uptake is achieved by deleting the inhibitory Mcub gene. Here we show that myofiber-specific Mcu deletion was not protective in

SUBMITTER: Bround MJ 

PROVIDER: S-EPMC10957967 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature