Reliance of ER–mitochondrial calcium signaling on mitochondrial EF-hand Ca2+ binding proteins: Miros, MICUs, LETM1 and solute carriers

Abstract

Endoplasmic reticulum (ER) and mitochondria are functionally distinct with regard to membrane protein biogenesis and oxidative energy production, respectively, but cooperate in several essential cell functions, including lipid biosynthesis, cell signaling and organelle dynamics. The interorganellar cooperation requires local communication that can occur at the strategically positioned and dynamic associations between ER and mitochondria. Calcium is locally transferred from ER to mitochondria at the associations and exerts regulatory effects on numerous proteins. A common Ca2+ sensing mechanism is the EF-hand Ca2+ binding domain, many of which can be found in proteins of the mitochondria, including Miro1&2, MICU1,2&3, LETM1 and mitochondrial solute carriers. Recently, these proteins have triggered much interest and were described in reports with diverging conclusions. The present essay focuses on their shared features and established specific functions.

Quantitative Changes in Gimap3 and Gimap5 Expression Modify Mitochondrial DNA Segregation in Mice

“…How then could a resident protein of the ER affect mtDNA segregation? Interactions between the ER and mitochondria play a key role in many aspects of mitochondrial homeostasis, such as morphology of the mitochondrial reticulum (division and tethering of the organelle), calcium handling, lipid transfer, and transmission of the mitochondrial genome among others (de Brito and Scorrano 2008;Kornmann et al 2009;Friedman et al 2011;Hoppins et al 2011;Connerth et al 2012;Rowland and Voeltz 2012;Korobova et al 2013;Hajnoczky et al 2014). Any number of these functions could be important to mtDNA segregation.…”

A novel chimeric aequorin fused with caveolin-1 reveals a sphingosine kinase 1-regulated Ca2+ microdomain in the caveolar compartment

“…For instance, recent reports have highlighted the importance of mitochondrial Ca 2+ handling in multiple (patho)physiological situations, and the long-sought molecular identity of the mitochondrial Ca 2+ uniporter (MCU) complex is now emerging [8][9][10][11]. Also, the importance of the interplay between the major Ca 2+ store, the endoplasmic reticulum (ER), and the mitochondria is being characterized [12,13]. Furthermore, the lysosomal compartments are involved in cellular Ca 2+ handling [14].…”

Calmodulin antagonists effect on Ca(2+) level in the mitochondria and cytoplasm of myometrium cells

“…Matrix acidification that occurs upon depolarization leads to the dissociation of these complexes, consequently, to an increase in the concentration of free Ca [2]. Secondly, it has been shown that the Ca 2+ -binding sites, so-called "EF hands", are part of the system that provide the cation metabolism in mito-експериментальні роботи chondria [5]. Therefore, the release of the cation may occur not only from the Ca 2+ -phosphate complexes but also from other binding sites.…”

“…Ca 2+ -CaM complex activates a series of enzymes and ion-transporting proteins. Some enzymes contain EF-hand motif directly in their structure [5]. It has been found that some mitochondria channels and transporters contain EF hands in their structure or are activated by the binding to Ca 2+ -CaM complex [5].…”

“…Some enzymes contain EF-hand motif directly in their structure [5]. It has been found that some mitochondria channels and transporters contain EF hands in their structure or are activated by the binding to Ca 2+ -CaM complex [5]. First of all it refers to the mitochondrial calcium uniporter, K + / H + /Ca 2+ exchangers, glutamate/aspartate transporter and others [5].…”