Molecular Tuning of the Axonal Mitochondrial Ca2+ Uniporter Ensures Metabolic Flexibility of Neurotransmission

Neuron, Год журнала: 2019, Номер 105(4), С. 678 - 687.e5

Опубликована: Дек. 17, 2019

Язык: Английский

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Regulation of the ER stress response by a mitochondrial microprotein

Nature Communications, Год журнала: 2019, Номер 10(1)

Опубликована: Окт. 25, 2019

Abstract Cellular homeostasis relies on having dedicated and coordinated responses to a variety of stresses. The accumulation unfolded proteins in the endoplasmic reticulum (ER) is common stress that triggers conserved pathway called protein response (UPR) mitigates damage, dysregulation UPR underlies several debilitating diseases. Here, we discover previously uncharacterized 54-amino acid microprotein PIGBOS regulates UPR. localizes mitochondrial outer membrane where it interacts with ER CLCC1 at ER–mitochondria contact sites. Functional studies reveal loss leads heightened increased cell death. characterization reveals an undiscovered role for protein, this case microprotein, regulation originating ER. This study demonstrates microproteins be unappreciated class genes are critical inter-organelle communication, homeostasis, survival.

Язык: Английский

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Dysregulation of mitochondria-lysosome contacts by GBA1 dysfunction in dopaminergic neuronal models of Parkinson’s disease

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Март 22, 2021

Abstract Mitochondria-lysosome contacts are recently identified sites for mediating crosstalk between both organelles, but their role in normal and diseased human neurons remains unknown. In this study, we demonstrate that mitochondria-lysosome can dynamically form the soma, axons, dendrites of neurons, allowing bidirectional crosstalk. Parkinson’s disease patient derived harboring mutant GBA1 exhibited prolonged due to defective modulation untethering protein TBC1D15, which mediates Rab7 GTP hydrolysis contact untethering. This dysregulation was decreased (β-glucocerebrosidase (GCase)) lysosomal enzyme activity could be rescued by increasing with a GCase modulator. These defects resulted disrupted mitochondrial distribution function, further TBC1D15 -linked neurons. Together, our work demonstrates potential as an upstream regulator function dynamics midbrain dopaminergic disease.

Язык: Английский

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Organelle-level precision with next-generation targeting technologies

Nature Reviews Materials, Год журнала: 2021, Номер 7(5), С. 355 - 371

Опубликована: Ноя. 23, 2021

Язык: Английский

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Mitochondria Associated Membranes (MAMs): Architecture and physiopathological role

Cell Calcium, Год журнала: 2021, Номер 94, С. 102343 - 102343

Опубликована: Янв. 2, 2021

Язык: Английский

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