The IP3 receptor–mitochondria connection in apoptosis and autophagy

Abstract

The amount of Ca(2+) taken up in the mitochondrial matrix is a crucial determinant of cell fate; it plays a decisive role in the choice of the cell between life and death. The Ca(2+) ions mainly originate from the inositol 1,4,5-trisphosphate (IP(3))-sensitive Ca(2+) stores of the endoplasmic reticulum (ER). The uptake of these Ca(2+) ions in the mitochondria depends on the functional properties and the subcellular localization of the IP(3) receptor (IP(3)R) in discrete domains near the mitochondria. To allow for an efficient transfer of the Ca(2+) ions from the ER to the mitochondria, structural interactions between IP(3)Rs and mitochondria are needed. This review will focus on the key proteins involved in these interactions, how they are regulated, and what are their physiological roles in apoptosis, necrosis and autophagy. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.

Endoplasmic Reticulum Stress and Disrupted Neurogenesis in the Brain Are Associated with Cognitive Impairment and Depressive-Like Behavior after Spinal Cord Injury

“…However, when ER stress is prolonged or too severe, these mechanisms fail to restore proteostasis leading to cell death. [77][78][79] This may explain that mild injury did not affect neuronal survival, as well as total number of activated microglia in the brain. ER stress significantly increases in an injury …”

Fragmented Inositol 1,4,5-Trisphosphate Receptors Retain Tetrameric Architecture and Form Functional Ca2+ Release Channels

“…Apoptosis is an evolutionary conserved process vital for normal development and is also implicated in the etiology of many human diseases. Notably, many current cellular models of apoptosis posit that prolonged and sustained elevations of the intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i )can be an important event for the initiation and/or progression of the apoptotic cascade (14,15). Moreover, numerous reports have suggested that altered IP 3 R activity is involved in apoptosis in a variety of cell types (reviewed in Ref.…”

Maternal obesity in mice not only affects fresh embryo quality but also aggravates injury due to vitrification

“…The ER lumen stores a 1000-fold excess of Ca 2+ compared with cytosol and, when stressed, releases Ca 2+ , thereby evoking Ca 2+ signaling, which then critically affects mitochondrial function [31]. ER Ca 2+ release and subsequent Ca 2+ uptake by mitochondria and excessive fuel (carbohydrates and fatty acids) within the obese reproductive environment result in Fig.…”

“…n = 3 pools of embryos per group. Different superscript letters indicate significant differences by one-way ANOVA, followed by Tukey's post hoc test; P < 0.05 increasing production of reactive oxygen species, uncoupling of oxidative phosphorylation, matrix swelling, and subsequent release of various apoptotic factors, including cytochrome C and effector caspases that lead to cellular apoptosis [26,31]. In embryos from obese mice, we found that significantly higher MnSOD (in day-5 blastocysts) expression levels exist in mitochondria for the conversion of superoxide to hydrogen peroxide.…”