Pathological consequences of MICU1 mutations on mitochondrial calcium signalling and bioenergetics

Calcium is utilised by cells in signalling and in regulating ATP production; it also contributes to cell survival and, when concentrations are unbalanced, triggers pathways for cell death. Mitochondria contribute to calcium buffering, meaning that mitochondrial calcium uptake and release is intimately related to cytosolic calcium concentrations. This review focuses on the proteins contributing to mitochondrial calcium homoeostasis, the roles of the mitochondrial permeability transition pore (MPTP) and mitochondrial calcium-activated proteins, and their relevance in neurodegenerative pathologies. It also covers alterations to calcium homoeostasis in Friedreich ataxia (FA).

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P24 Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium signalling

Neuromuscular Disorders ◽

10.1016/s0960-8966(14)70040-9 ◽

2014 ◽

Vol 24 ◽

pp. S13

Author(s):

J.A. Sharpe ◽

C.V. Logan ◽

G. Szabadkai ◽

D.A. Parry ◽

S. Torelli ◽

...

Keyword(s):

Calcium Signalling ◽

Mitochondrial Calcium ◽

Loss Of Function ◽

Muscle Disorder

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Mitochondrial calcium signalling in cell death

FEBS Journal ◽

10.1111/j.1742-4658.2005.04855.x ◽

2005 ◽

Vol 272 (16) ◽

pp. 4013-4022 ◽

Cited By ~ 20

Author(s):

Sara Leo ◽

Katiuscia Bianchi ◽

Marisa Brini ◽

Rosario Rizzuto

Keyword(s):

Cell Death ◽

Calcium Signalling ◽

Mitochondrial Calcium

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Bcl-2 Family of Proteins in the Control of Mitochondrial Calcium Signalling: An Old Chap with New Roles

International Journal of Molecular Sciences ◽

10.3390/ijms22073730 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3730

Author(s):

Jordan L. Morris ◽

Germain Gillet ◽

Julien Prudent ◽

Nikolay Popgeorgiev

Keyword(s):

Cell Death ◽

Cell Migration ◽

Cell Survival ◽

Calcium Signalling ◽

Mitochondrial Pathway ◽

Signalling Pathways ◽

Mitochondrial Outer Membrane ◽

Mitochondrial Calcium ◽

New Class ◽

Mitochondrial Outer Membrane Permeabilization

Bcl-2 family proteins are considered as one of the major regulators of apoptosis. Indeed, this family is known to control the mitochondrial outer membrane permeabilization (MOMP): a central step in the mitochondrial pathway of apoptosis. However, in recent years Bcl-2 family members began to emerge as a new class of intracellular calcium (Ca2+) regulators. At mitochondria-ER contacts (MERCs) these proteins are able to interact with major Ca2+ transporters, thus controlling mitochondrial Ca2+ homeostasis and downstream Ca2+ signalling pathways. Beyond the regulation of cell survival, this Bcl-2-dependent control over the mitochondrial Ca2+ dynamics has far-reaching consequences on the physiology of the cell. Here, we review how the Bcl-2 family of proteins mechanistically regulate mitochondrial Ca2+ homeostasis and how this regulation orchestrates cell death/survival decisions as well as the non-apoptotic process of cell migration.

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