Calcium signaling in mitochondrial intermembrane space.

Biochem Soc Trans

Department of Internal Medicine, Section of Cardiovascular Medicine, Section of Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, U.S.A.

Published: October 2024

AI Article Synopsis

  • * IMS contains proteins that are important for triggering apoptosis and managing reactive oxygen species, influencing mitochondrial energy production and cell death pathways through calcium (Ca2+) regulation.
  • * The review focuses on different Ca2+ sensors located in the IMS, their mechanisms of action, and how they relate to health conditions and diseases, highlighting their unique properties and functions.

Article Abstract

The mitochondrial intermembrane space (IMS) is a highly protected compartment, second only to the matrix. It is a crucial bridge, coordinating mitochondrial activities with cellular processes such as metabolites, protein, lipid, and ion exchange. This regulation influences signaling pathways for metabolic activities and cellular homeostasis. The IMS harbors various proteins critical for initiating apoptotic cascades and regulating reactive oxygen species production by controlling the respiratory chain. Calcium (Ca2+), a key intracellular secondary messenger, enter the mitochondrial matrix via the IMS, regulating mitochondrial bioenergetics, ATP production, modulating cell death pathways. IMS acts as a regulatory site for Ca2+ entry due to the presence of different Ca2+ sensors such as MICUs, solute carriers (SLCs); ion exchangers (LETM1/SCaMCs); S100A1, mitochondrial glycerol-3-phosphate dehydrogenase, and EFHD1, each with unique Ca2+ binding motifs and spatial localizations. This review primarily emphasizes the role of these IMS-localized Ca2+ sensors concerning their spatial localization, mechanism, and molecular functions. Additionally, we discuss how these sensors contribute to the progression and pathogenesis of various human health conditions and diseases.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727339PMC
http://dx.doi.org/10.1042/BST20240319DOI Listing

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