Partial loss of MCU mitigates pathology in vivo across a diverse range of neurodegenerative disease models.

Mitochondrial calcium (Ca) uptake augments metabolic processes and buffers cytosolic Ca levels; however, excessive mitochondrial Ca can cause cell death. Disrupted mitochondrial function and Ca homeostasis are linked to numerous neurodegenerative diseases (NDs), but the impact of mitochondrial Ca disruption is not well understood. Here, we show that Drosophila models of multiple NDs (Parkinson's, Huntington's, Alzheimer's, and frontotemporal dementia) reveal a consistent increase in neuronal mitochondrial Ca levels, as well as reduced mitochondrial Ca buffering capacity, associated with increased mitochondria-endoplasmic reticulum contact sites (MERCs).

Comprehensive Genetic Characterization of Mitochondrial Ca Uniporter Components Reveals Their Different Physiological Requirements In Vivo.

Mitochondrial Ca uptake is an important mediator of metabolism and cell death. Identification of components of the highly conserved mitochondrial Ca uniporter has opened it up to genetic analysis in model organisms. Here, we report a comprehensive genetic characterization of all known uniporter components conserved in Drosophila.