Uncontrolled mitochondrial calcium uptake underlies the pathogenesis of neurodegeneration in MICU1-deficient mice and patients.

ABSTRACT: Dysregulation of mitochondrial Ca²⁺ homeostasis has been linked to neurodegenerative diseases. Mitochondrial Ca²⁺ uptake is mediated via the calcium uniporter complex that is primarily regulated by MICU1, a Ca²⁺-sensing gatekeeper. Recently, human patients with MICU1 loss-of-function mutations were diagnosed with neuromuscular and cognitive impairments. While studies in patient-derived cells revealed altered mitochondrial calcium signaling, the neuronal pathogenesis was difficult to study. To fill this void, we created a neuron-specific MICU1-KO mouse model. These animals show progressive, abnormal motor and cognitive phenotypes likely caused by the degeneration of motor neurons in the spinal cord and the cortex. We found increased susceptibility to mitocho

SUBMITTER: Singh R 

PROVIDER: S-EPMC8932652 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature