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D'Angelo, D.* ; Vecellio Reane, D. ; Raffaello, A.*

Neither too much nor too little: Mitochondrial calcium concentration as a balance between physiological and pathological conditions.

Front. Mol. Biosci. 10:1336416 (2023)

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Ca²⁺ ions serve as pleiotropic second messengers in the cell, regulating several cellular processes. Mitochondria play a fundamental role in Ca²⁺ homeostasis since mitochondrial Ca²⁺ (mitCa²⁺) is a key regulator of oxidative metabolism and cell death. MitCa²⁺ uptake is mediated by the mitochondrial Ca²⁺ uniporter complex (MCUc) localized in the inner mitochondrial membrane (IMM). MitCa²⁺ uptake stimulates the activity of three key enzymes of the Krebs cycle, thereby modulating ATP production and promoting oxidative metabolism. As Paracelsus stated, "Dosis sola facit venenum,"in pathological conditions, mitCa²⁺ overload triggers the opening of the mitochondrial permeability transition pore (mPTP), enabling the release of apoptotic factors and ultimately leading to cell death. Excessive mitCa²⁺ accumulation is also associated with a pathological increase of reactive oxygen species (ROS). In this article, we review the precise regulation and the effectors of mitCa²⁺ in physiopathological processes.

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Publication type Article: Journal article

Document type Review

Corresponding Author

Keywords Calcium ; Cell Death ; Metabolism ; Mitochondria ; Mitochondrial Calcium Uniporter (mcu); Inositol 1,4,5-trisphosphate Receptors; Pyruvate-dehydrogenase Phosphatase; Linked Isocitrate Dehydrogenase; Endoplasmic-reticulum Ca2+; 2-oxoglutarate Dehydrogenase; Signal Transmission; Adenine-nucleotides; Essential Component; Ca-2+ Ions; Rat-heart

ISSN (print) / ISBN 2296-889X

e-ISSN 2296-889X

Journal Frontiers in Molecular Biosciences

Quellenangaben Volume: 10, Article Number: 1336416

Publisher Frontiers

Publishing Place Lausanne

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Obesity (IDO)

Grants European Union
European Union (Next-Generation EU)
Italian Ministry of University and Research