Biomaterial Database

Pharmacological modulation of mitochondrial calcium homeostasis. 2018

Daniela M Arduino, and Fabiana Perocchi

Gene Center, Department of Biochemistry, Ludwig-Maximilians Universität München, Munich, 81377, Germany.

Mitochondria are pivotal organelles in calcium (Ca2+ ) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca2+ homeostasis have been linked to a variety of pathological conditions and are critical in the aetiology of several human diseases. Efforts have been taken to harness mitochondrial Ca2+ transport mechanisms for therapeutic intervention, but pharmacological compounds that direct and selectively modulate mitochondrial Ca2+ homeostasis are currently lacking. New avenues have, however, emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca2+ influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca2+ homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progress towards a systems-level pharmacological targeting of mitochondrial Ca2+ homeostasis.

UI	MeSH Term	Description	Entries
D008928	Mitochondria	Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)	Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D006706	Homeostasis	The processes whereby the internal environment of an organism tends to remain balanced and stable.	Autoregulation
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D024101	Mitochondrial Proteins	Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.	Proteins, Mitochondrial,Mitochondrial Protein,Protein, Mitochondrial
D028361	Mitochondrial Diseases	Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.	Electron Transport Chain Deficiencies, Mitochondrial,Mitochondria Dysfunction,Mitochondrial Defect,Mitochondrial Dysfunction,Oxidative Phosphorylation Deficiencies,Respiratory Chain Deficiencies, Mitochondrial,Mitochondrial Disorders,Mitochondrial Electron Transport Chain Deficiencies,Mitochondrial Respiratory Chain Deficiencies,Defect, Mitochondrial,Deficiency, Oxidative Phosphorylation,Disease, Mitochondrial,Disorder, Mitochondrial,Dysfunction, Mitochondria,Dysfunction, Mitochondrial,Mitochondria Dysfunctions,Mitochondrial Defects,Mitochondrial Disease,Mitochondrial Disorder,Mitochondrial Dysfunctions,Oxidative Phosphorylation Deficiency,Phosphorylation Deficiency, Oxidative